Science.gov

Sample records for 10-14 cm3 s-1

  1. 24 CFR 10.14 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Hearings. 10.14 Section 10.14 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development RULEMAKING: POLICY AND PROCEDURES Procedures § 10.14 Hearings. (a) The provisions of 5 U.S.C. 556 and...

  2. Adaptation of California Measure of Mental Motivation-CM3

    ERIC Educational Resources Information Center

    Özdemir, Hasan Fehmi; Demirtasli, Nükhet Çikrikçi

    2015-01-01

    Education without doubt, plays a vital role for individuals to gain the essential personal traits of the 21st century, also known as "knowledge age". One of the most important skills among these fundamental qualities which the individuals should be equipped with is critical thinking. California Measure of Mental Motivation-CM3 was…

  3. 15 CFR 10.14 - Appeals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PRODUCT STANDARDS § 10.14 Appeals. (a) Any person directly affected by a procedural action taken by NIST..., by NIST or the Standing Committee under § 10.10 regarding the review of a published standard, or... action complained of (NIST, the Standard Review Committee, or the Standing Committee) within 30...

  4. The amino acid sequence of protein CM-3 from Dendroaspis polylepis polylepis (black mamba) venom.

    PubMed

    Joubert, F J

    1985-01-01

    Protein CM-3 from Dendroaspis polylepis polylepis venom was purified by gel filtration and ion exchange chromatography. It comprises 65 amino acids including eight half-cystines. The complete amino acid sequence of protein CM-3 has been elucidated. The sequence (residues 1-50) resembles that of the N-terminal sequence of the subunits of a synergistic type protein and residues 51-65 that of the C-terminal sequence of an angusticeps type protein. Mixtures of protein CM-3 and angusticeps type proteins showed no apparent synergistic effect, in that their toxicity in combination was no greater than the sum of their individual toxicities.

  5. Smart-power integrated circuits to drive piezoelectric actuators for a cm3 microrobot system

    NASA Astrophysics Data System (ADS)

    Puig-Vidal, Manel; Lopez-Sanchez, J.; Miribel-Catala, P.; Montane, Enric; Bota, Sebastian A.; Samitier, Josep; Simu, Urban; Johansson, Stefan A. I.

    2001-08-01

    Today, the use of robots for self acting tasks in applications ranging from biology and medicine to microsystems technology demand miniaturized dimensions and high-precision handling techniques. A lot of these tasks have been carried out by humans, but the manual capabilities are restricted to certain tolerances. Transport and manipulation of biological cells or assembly of micromechanical parts are the best suited applications for microrobots with sizes about cm3. Low cost and high-resolution actuators are critical performances which determine to choose piezoceramic materials as more suitable for micropositioning and micromanipulation units of a cm3 microrobot. Smart Piezoactuator Unit (SPUs) as a basic element of a new generation of cm3 microrobots have been developped. The main characteristic of this proposed Smart Piezoactuator Unit system is the integration of driving circuitry with the piezoelectric actuators and to include a serial communication interface to minimize the number of power and command wires. Micropositioning and micromanipulation units are developed combining properly 6 Smart Piezoactuator Units each one. A BCD technology (Bipolar, CMOS, DMOS) is used to design high voltage smart power integrated circuit for these Smart Piezoactuator Units. Using this technology we integrate in the same chip 4 power drivers with its control and protection circuitry.

  6. Accuracy of free energies of hydration using CM1 and CM3 atomic charges.

    PubMed

    Udier-Blagović, Marina; Morales De Tirado, Patricia; Pearlman, Shoshannah A; Jorgensen, William L

    2004-08-01

    Absolute free energies of hydration (DeltaGhyd) have been computed for 25 diverse organic molecules using partial atomic charges derived from AM1 and PM3 wave functions via the CM1 and CM3 procedures of Cramer, Truhlar, and coworkers. Comparisons are made with results using charges fit to the electrostatic potential surface (EPS) from ab initio 6-31G* wave functions and from the OPLS-AA force field. OPLS Lennard-Jones parameters for the organic molecules were used together with the TIP4P water model in Monte Carlo simulations with free energy perturbation theory. Absolute free energies of hydration were computed for OPLS united-atom and all-atom methane by annihilating the solutes in water and in the gas phase, and absolute DeltaGhyd values for all other molecules were computed via transformation to one of these references. Optimal charge scaling factors were determined by minimizing the unsigned average error between experimental and calculated hydration free energies. The PM3-based charge models do not lead to lower average errors than obtained with the EPS charges for the subset of 13 molecules in the original study. However, improvement is obtained by scaling the CM1A partial charges by 1.14 and the CM3A charges by 1.15, which leads to average errors of 1.0 and 1.1 kcal/mol for the full set of 25 molecules. The scaled CM1A charges also yield the best results for the hydration of amides including the E/Z free-energy difference for N-methylacetamide in water.

  7. Improvement of surface albedo parameterization within a regional climate model (RegCM3)

    NASA Astrophysics Data System (ADS)

    Bao, Y.; Lü, S.

    2009-03-01

    A parameterization for calculating surface albedo of Solar Zenith Angel (SZA) dependence with coefficient for each vegetation type determined on the Moderate Resolution Imaging Spectro-radiometer (MODIS) reformed by the Bidirectional Reflectance Distribution Function (BRDF) is incorporated within the latest Abdus Salam International Centre for Theoretical Physics (ICTP) Regional Climate Model (RegCM3), and evaluated with a high resolution one-way nesting simulation in China using the Climate Research Unit (CRU) data and the observations from the Field Experiment on Interaction between Land and Atmosphere in Arid Region of Northwest China (NWC-ALIEX). The performance of the SZA method modeling surface characteristic is investigated.Results indicate, RegCM with SZA method (RCM_SZA) considerably improve the cold bias of original RegCM (RCM_ORI) in air surface temperature in East Asia with 1.2 degree increased in summer due to the lower albedo produced by SZA method which makes more solar radiation absorbed by the surface and used for heating the atmosphere near to the surface. The simulated diurnal cycle of ground temperature conforms fairly well to the observation in the nesting simulation in Northwest China, especially during the noon time when the SZA has the lowest value. However, the modification can not obviously affect the East Asia summer monsoon precipitation simulation although RCM_SZA produce more evapo-transpiration in surface with more than 2 Wm-2 increases in simulated latent heat fluxes both in East Asia and in Northwest China compared to RCM_ORI.

  8. Evaluation and analysis of RegCM3 simulated summer rainfall over the Huaihe River Basin of China

    NASA Astrophysics Data System (ADS)

    Zong, Peishu; Wang, Huijun

    2011-06-01

    This study evaluates the ability of the Abdus Salam International Center for Theoretical Physics (ICTP) version 3 Regional Climate Model (RegCM3) in simulating the summer rainfall amount and distribution and large-scale circulation over the Huaihe River basin of China. We conducted the simulation for the period of 1982-2001 and the wet year of 2003 to test the ensemble simulation capacity of RegCM3. First, by comparing the simulated rainfall amount and distribution against the observations, it is found that RegCM3 can reproduce the rainfall pattern and its annual variations. In addition, the simulated spatial patterns of 850-hPa wind and specific humidity fields are close to the observations, although the wind speed and humidity values are larger. Finally, the ensemble simulation of RegCM3 for summer 2003 failed to capture the spatial distribution and underestimated the magnitude of the precipitation anomalies, and the reasons are analyzed.

  9. High resolution climate change simulation of the 21st century over East Asia by RegCM3

    NASA Astrophysics Data System (ADS)

    Gao, Xuejie

    2010-05-01

    To meet the increasing demands from the climate change impact assessment studies, a high resolution climate change simulation over East Asia region has being performed in the National Climate Center of the China Meteorological Administration. The model employed in the study is the Abdus Salam International Centre for Theoretical Physics (ICTP) Regional Climate Model (RegCM3). A global model of the CCSR/NIES/FRCGC MIROC3.2_hires is selected to drive RegCM3 because of its high resolution (T106) and its good performances in simulating the present day climate over the region. The simulation is conducted at 25-km grid spacing for the period of 1951-2100. Observed CO2 concentration are used for the present day simulation of 1951-2000 and the emission scenario of IPCC SRES A1B is used as the GHG (greenhouse gases) forcing. Simulations of present day climate over China by RegCM3 and MIROC3.2_hires are compared against observation to valid the model performances. Results show that both models reproduced the general pattern of surface air temperature and precipitation well over the region. Compared to the driving MIROC3.2_hires, RegCM3 provides with more spatial details of the surface fields. Differed from previous GCM-RegCM3 simulations, the RegCM3 did not improves the general pattern of the precipitation due to the good performances of MIROC3.2_hires. Preliminary analysis of the future changes simulated by the two models' show difference, in particular during June-July-August. For example while the MIROC3.2_hires projected a prevailing increase of precipitation in JJA over China, the RegCM3 projected extended areas of decreased precipitation. The data are available for those interested from the community of climate change impacts studies.

  10. Hn PAHs and the 2940 and 28050/cm (3.40 and 3.51 Microns) Infrared Emission Features

    NASA Technical Reports Server (NTRS)

    Bernstein, Max; Sandford, Scott; Allamandola, Louis; Witteborn, Fred (Technical Monitor)

    1996-01-01

    The 3150-2700/cm (3.17-3.70 microns) range of the spectra of a number of Ar matrix isolated PAHs containing excess H atoms (Hn-PAHs) are presented. This region covers features produced by aromatic and aliphatic C-H stretching vibrations as well as overtone and combination bands involving lower lying fundamentals. It is demonstrated that the aliphatic C-H stretches in molecules of this type having low-to-modest excess H coverage provide excellent fits to a number of the weak emission features superposed on the plateau between 3080 and 2700/cm (3.25 and 3.7 microns) in the spectra of many planetary nebulae, reflection nebulae, and HII regions. Higher H coverage is implied for a few objects. We compare these results in context with the other suggested identifications of the emission features in the 2950-2700/cm (3.39-3.70 microns) region and briefly discuss their astrophysical implications.

  11. Sensitivity of the GCM driven summer monsoon simulations to cumulus parameterization schemes in nested RegCM3

    NASA Astrophysics Data System (ADS)

    Sinha, P.; Mohanty, U. C.; Kar, S. C.; Dash, S. K.; Kumari, S.

    2013-04-01

    The regional climate model (RegCM3) from the Abdus Salam International Centre for Theoretical Physics has been used to simulate the Indian summer monsoon for three different monsoon seasons such as deficit (1987), excess (1988) and normal (1989). Sensitivity to various cumulus parameterization and closure schemes of RegCM3 driven by the National Centre for Medium Range Weather Forecasting global spectral model products has been tested. The model integration of the nested RegCM3 is conducted using 90 and 30-km horizontal resolutions for outer and inner domains, respectively. The India Meteorological Department gridded rainfall (1° × 1°) and National Centre for Environment Prediction (NCEP)-Department of Energy (DOE) reanalysis-2 of 2.5° × 2.5° horizontal resolution data has been used for verification. The RegCM3 forced by NCEP-DOE reanalysis-2 data simulates monsoon seasons of 1987 and 1988 reasonably well, but the monsoon season of 1989 is not represented well in the model simulations. The RegCM3 runs driven by the global model are able to bring out seasonal mean rainfall and circulations well with the use of the Grell and Anthes-Kuo cumulus scheme at 90-km resolution. While the rainfall intensity and distribution is brought out well with the Anthes-Kuo scheme, upper air circulation features are brought out better by the Grell scheme. The simulated rainfall distribution is better with RegCM3 using the MIT-Emanuel cumulus scheme for 30-km resolution. Several statistical analyses, such as correlation coefficient, root mean square error, equitable threat score, confirm that the performance of MIT-Emanuel scheme at 30-km resolution is better in simulating all-India summer monsoon rainfall. The RegCM3 simulated rainfall amount is more and closer to observations than that from the global model. The RegCM3 has corrected its driven GCM in terms of rainfall distribution and magnitude over some parts of India during extreme years. This study brings out several

  12. An Exploratory Pilot Study of the Strengthening Families Programme 10-14 (UK)

    ERIC Educational Resources Information Center

    Coombes, Lindsey; Allen, Deborah Mary; Foxcroft, David

    2012-01-01

    The Strengthening Families Programme 10-14 (SFP10-14; UK) is a seven-session DVD-based family skills training programme. While the programme has been extensively evaluated in the United States, no randomized controlled trial (RCT) of the SFP10-14 has been conducted in the United Kingdom. This exploratory Phase II study was an evaluation of a…

  13. 46 CFR 30.10-14 - Combination carrier-TB/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Combination carrier-TB/ALL. 30.10-14 Section 30.10-14 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-14 Combination carrier—TB/ALL. The term combination carrier means a tank vessel designed to...

  14. 46 CFR 30.10-14 - Combination carrier-TB/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Combination carrier-TB/ALL. 30.10-14 Section 30.10-14 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-14 Combination carrier—TB/ALL. The term combination carrier means a tank vessel designed to...

  15. New α-adrenergic property for synthetic MTβ and CM-3 three-finger fold toxins from black mamba.

    PubMed

    Blanchet, Guillaume; Upert, Gregory; Mourier, Gilles; Gilquin, Bernard; Gilles, Nicolas; Servent, Denis

    2013-12-01

    Despite their isolation more than fifteen years ago from the venom of the African mamba Dendroaspis polylepis, very few data are known on the functional activity of MTβ and CM-3 toxins. MTβ was initially classified as a muscarinic toxin interacting non-selectively and with low affinity with the five muscarinic receptor subtypes while no biological function was determined for CM-3. Recent results highlight the multifunctional activity of three-finger fold toxins for muscarinic and adrenergic receptors and reveal some discrepancies in the pharmacological profiles of their venom-purified and synthetic forms. Here, we report the pharmacological characterization of chemically-synthesized MTβ and CM-3 toxins on nine subtypes of muscarinic and adrenergic receptors and demonstrate their high potency for α-adrenoceptors and in particular a sub-nanomolar affinity for the α1A-subtype. Strikingly, no or very weak affinity were found for muscarinic receptors, highlighting that pharmacological characterizations of venom-purified peptides may be risky due to possible contaminations. The biological profile of these two homologous toxins looks like that one previously reported for the Dendroaspis angusticeps ρ-Da1a toxin. Nevertheless, MTβ and CM-3 interact more potently than ρ-Da1a with α1B- and α1D-AR subtypes. A computational analysis of the stability of the MTβ structure suggests that mutation S38I, could be involved in this gain in function.

  16. Outcomes in men with large prostates (≥ 60 cm(3)) treated with definitive proton therapy for prostate cancer.

    PubMed

    McGee, Lisa; Mendenhall, Nancy P; Henderson, Randal H; Morris, Christopher G; Nichols, Romaine C; Marcus, Robert J; Li, Zuofeng; Mendenhall, William M; Williams, Christopher R; Hoppe, Bradford S

    2013-04-01

    Large prostate size is associated with higher rates of genitourinary and gastrointestinal toxicities after definitive treatment for prostate cancer, and because of this many men will undergo cytoreduction with androgen deprivation therapy (ADT) before definitive therapy, which results in its own unique toxicities and worsens quality of life. This series investigates genitourinary and gastrointestinal toxicity in men with large prostates (> 60 cm(3)) undergoing definitive proton therapy (PT) for prostate cancer. Material and methods. From 2006 to 2010, 186 men with prostates ≥ 60 cm(3) were treated with definitive PT (median dose, 78 CGE) for low- (47%), intermediate- (37%) and high-risk (16%) prostate cancer. Median prostate size was 76 cm(3) (range, 60-143 cm(3)) and pretreatment IPSS was > 15 in 27%. At baseline, 51% were managed for obstructive symptoms with transurethral resection of the prostate (TURP) (9.7%) or medical management with α blockers (32%), 5 α-reductase inhibitors (15%), and/or saw palmetto (11%). Fourteen men received ADT for cytoreduction. Results. Median follow-up was two years. Grade 3 genitourinary toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). Multivariate analysis demonstrated pretreatment medical management (p = 0.0065) and pretreatment TURP (p = 0.0002) were significantly associated with grade 3 genitourinary toxicity. One man experienced grade 3 gastrointestinal toxicity and 15 men had grade 2 gastrointestinal toxicities. On multivariate analysis, dose > 78 CGE was associated with increased grade 2 + gastrointestinal toxicity (p = 0.0142). Conclusion. Definitive management of men with large prostates without ADT was associated with low rates of genitourinary and gastrointestinal toxicity.

  17. Tellurite-, tellurate-, and selenite-based anaerobic respiration by strain CM-3 isolated from gold mine tailings.

    PubMed

    Maltman, Chris; Piercey-Normore, Michele D; Yurkov, Vladimir

    2015-09-01

    The newly discovered strain CM-3, a Gram-negative, rod-shaped bacterium from gold mine tailings of the Central Mine in Nopiming Provincial Park, Canada, is capable of dissimilatory anaerobic reduction of tellurite, tellurate, and selenite. CM-3 possesses very high level resistance to these oxides, both aerobically and anaerobically. During aerobic growth, tellurite and tellurate resistance was up to 1500 and 1000 µg/ml, respectively. In the presence of selenite, growth occurred at the highest concentration tested, 7000 µg/ml. Under anaerobic conditions, resistance was decreased to 800 µg/ml for the Te oxides; however, much like under aerobic conditions, growth with selenite still took place at 7000 µg/ml. In the absence of oxygen, CM-3 couples oxide reduction to an increase in biomass. Following an initial drop in viable cells, due to switching from aerobic to anaerobic conditions, there was an increase in CFU/ml greater than one order of magnitude in the presence of tellurite (6.6 × 10(3)-8.6 × 10(4) CFU/ml), tellurate (4.6 × 10(3)-1.4 × 10(5) CFU/ml), and selenite (2.7 × 10(5)-5.6 × 10(6) CFU/ml). A control culture without metalloid oxides showed a steady decrease in CFU/ml with no recovery. ATP production was also increased in the presence of each oxide, further indicating anaerobic respiration. Partial 16S rRNA gene sequencing revealed a 99.0 % similarity of CM-3 to Pseudomonas reactans.

  18. Sensitivity of simulated extreme precipitation and temperature to convective parameterization using RegCM3 in China

    NASA Astrophysics Data System (ADS)

    Hui, Pinhong; Tang, Jianping; Wang, Shuyu; Wu, Jian

    2015-10-01

    In this study, the regional climate model of RegCM3 is applied to investigate the sensitivity of regional climate over China using four cumulus parameterizations, the modified Anthes-Kuo (AK), the Grell with Arakawa-Schubert closure, the Grell with Fritsch-Chappell closure, and the MIT-Emanuel (EM). The model was integrated over the period of 1982 to 2001 using the NCEP Reanalysis data NNRP2 as boundary conditions. RegCM3 coupled with various cumulus parameterizations is evaluated firstly as for its ability to represent regional climatology and climate extreme indices, and the results show that simulated regional climate in China is sensitive to the option of cumulus parameterizations. All the cumulus schemes produce a northward expansion of heavy rain area and an underestimation of surface air temperature. For precipitation, the AK scheme simulates relatively better magnitude, while the EM scheme has more reliable performance on the spatial distribution. RegCM3 can represent the spatial distributions of extreme indices for both precipitation and temperature, as well as their decadal trends irrelevant to the cumulus parameterizations. However, the model underestimates the consecutive dry days and overestimates the three extreme wet indices, with the EM scheme giving the worst result. Slight underestimations of extreme temperature indices are detected in all cumulus parameterization scheme runs. The shapes of probability distribution functions for extreme indices are correctly produced, though the probabilities of extreme dry and warm events are underestimated.

  19. Perovskite CH3NH3PbI3(Cl) Single Crystals: Rapid Solution Growth, Unparalleled Crystalline Quality, and Low Trap Density toward 10(8) cm(-3).

    PubMed

    Lian, Zhipeng; Yan, Qingfeng; Gao, Taotao; Ding, Jie; Lv, Qianrui; Ning, Chuangang; Li, Qiang; Sun, Jia-Lin

    2016-08-03

    Single crystal reflects the intrinsic physical properties of a material, and single crystals with high-crystalline quality are highly desired for the acquisition of high-performance devices. We found that large single crystals of perovskite CH3NH3PbI3(Cl) could be grown rapidly from chlorine-containing solutions. Within 5 days, CH3NH3PbI3(Cl) single crystal as large as 20 mm × 18 mm × 6 mm was harvested. As a most important index to evaluate the crystalline quality, the full width at half-maximum (fwhm) in the high-resolution X-ray rocking curve (HR-XRC) of as-grown CH3NH3PbI3(Cl) single crystal was measured as 20 arcsec, which is far superior to so far reported CH3NH3PbI3 single crystals (∼1338 arcsec). The unparalleled crystalline quality delivered a low trap-state density of down to 7.6 × 10(8) cm(-3), high carrier mobility of 167 ± 35 cm(2) V(-1) s(-1), and long transient photovoltaic carrier lifetime of 449 ± 76 μs. The improvement in the crystalline quality, together with the rapid growth rate and excellent carrier transport property, provides state-of-the-art single crystalline hybrid perovskite materials for high-performance optoelectronic devices.

  20. Drug Ingestions in Children 10-14 Years Old: An Old Problem Revisited

    ERIC Educational Resources Information Center

    Pomerantz, Wendy; Gittelman, Michael; Farris, Sarah; Frey, Lauren

    2009-01-01

    To determine changes in rates of drug ingestions in 10-14 year old children in our country, a retrospective chart review of 10-14 year olds hospitalized for drug ingestion between 1993-1995 and 2000-2004 was performed. Odds ratios and Chi-square were used for analyses. From 1993-1995 there were 92.8 ingestions/100,000 children/year; from 2000-2004…

  1. Regional Climate Responses To Planetary-Scale Geoengineering Activities, as Modeled Using climateprediction.net/HadCM3L

    NASA Astrophysics Data System (ADS)

    Ricke, K.

    2009-12-01

    Concerns that climate mitigation is occurring too slowly, or that there may be a rapid "climate surprise," have lead to renewed dialogue within the scientific community about cooling the planet through geoengineering, specifically stratospheric albedo modification (SAM). There is little consensus about regional hydrological effects of such activities despite a recent spate of climate modeling studies looking at its potential impacts. Here we present the results from one large-ensemble experiment that used Hadley Centre Coupled Model, version 3 with reduced resolution over the ocean (HadCM3L), implemented through climateprediction.net. The analysis examines 54 globally-uniform stratospheric optical depth modification scenarios designed to stabilize global temperatures under SRES A1B. We present normalized regional temperature anomalies versus normalized regional precipitation and subsurface runoff anomalies (for example, see Figure 1) and the results of regression analyses to quantify the relationships between level of stratospheric optical property modification (i.e., geoengineering) and regional hydrology. Results show that while such shortwave compensations for longwave anthropogenic forcings does generally return regional climates to closer to their baseline climate states than the no-geoengineering, business-as-usual scenarios, the magnitudes and sensitivities of regional responses to this type of activity, as modeled in HadCM3L, are highly variable. Regions, such as Eastern China and India, migrate away from their baseline climate states in different ways, illustrating the impossibility of simultaneous stabilization of regional climates. The linearity of the effect of incrementally increasing stratospheric optical depth also varies regionally. Figure 1: Normalized regional temperature and precipitation anomalies (<2020s>-<1990s> and <2070s>-<1990s>) in units of baseline standard deviations for each region). Each grayscale point in-series near the origin

  2. High-resolution δ13C measurements on ancient air extracted from less than 10 cm3 of ice

    NASA Astrophysics Data System (ADS)

    Leuenberger, M. C.; Eyer, M.; Nyfeler, P.; Stauffer, B.; Stocker, T. F.

    2003-04-01

    A new method for δ13C analysis of very small air amounts of less than 0.5 cm3 STP was developed. This corresponds to less than 10 g of ice. It is based on the needle-crasher technique, which is routinely used for CO2 concentration measurements by infrared laser absorption. The extracted air is slowly expanded into a large volume through a water trap held at -70 °C where the pressure is measured. This sampled air is then carried by a high helium flux through a preconcentration system to separate CO2 cryogenically from the air. The small CO2 amount is then released into a low helium stream which forces the CO2 via an open split device to a mass spectrometer. The overall precision, based on replicates of standard air without crushing, is significantly better than 0.1‰ for a single analysis, and is further improved by a triplicate measurement of the same sample through a specially designed gas splitter. Performing δ13C measurements on ice air through the whole system, we reach a reproducibility of 0.12‰. Additional information is obtained through amplitude vs. pressure ratio determination, which results in a good control of the CO2 concentration (1 ppm precision for 1σ). The new method allows us to produce highly resolved records of atmospheric δ13C from air enclosed in ice, which is required to better understand the evolution and the temporal variability of the global carbon cycle.

  3. Particle- and gas-phase emissions of polycyclic aromatic hydrocarbons from two-stroke, 50-cm 3 mopeds

    NASA Astrophysics Data System (ADS)

    Spezzano, Pasquale; Picini, Paolo; Cataldi, Dario; Messale, Fabrizio; Manni, Claudio

    2008-06-01

    The emissions of gas- and particle-phase polycyclic aromatic hydrocarbons (PAHs) were evaluated in the exhaust of 10 mopeds (4 EURO-0, 4 EURO-1 and 2 EURO-2) equipped with two-stroke engines with displacement of 50 cm3. Sampling was performed on a dynamometer bench both during the "cold-start" and the "hot" phases of the ECE-47 driving cycle. Eighteen PAHs were quantified and total PAH emission factors (∑PAH) ranged from 1790 to 15,059 μg km-1. Expressed in benzo(a)pyrene equivalent (BaPeq), emission factors ranged 4.7-86.3 μg km-1. PAH emissions are reduced according to the legislation class: EURO-0>EURO-1>EURO-2. PAH emission factors were greater during the cold-start phase than the hot phase of the ECE-47 cycle. Results show that despite their small engine size, two-stroke mopeds can emit amounts of particulate PAHs comparable or even higher than PAH emissions reported elsewhere from gasoline- and diesel-powered passenger cars and light- and heavy-duty vehicles.

  4. Cultural accommodation of the Strengthening Families Programme 10-14: UK Phase I study.

    PubMed

    Allen, Debby; Coombes, Lindsey; Foxcroft, David R

    2007-08-01

    Social and cultural differences between the United States and the United Kingdom mean that positive results from US prevention programmes may not translate to the United Kingdom. The Strengthening Families Programme 10-14 (SFP10-14) has been evaluated in a large Phase III randomized controlled trial in rural Iowa in the United States and shown to be effective for delaying alcohol and drug initiation. This paper reports the first stage of the adaptation and evaluation of the SFP10-14 for the United Kingdom through a process of cultural accommodation of the SFP10-14 materials and format. Themes that emerged in nominal group and focus group research with young people and their parents indicated that changes to the US SFP10-14 materials needed to consider language, narrators, realism, acceptability of exercises/games, perceived religiosity and ethnic representativeness. However, not all changes reflected straightforward cultural differences, as adaptations were also required to improve the quality and to update the material, indicating that cultural accommodation does not necessarily imply cultural diversity.

  5. The eastern Tropical Pacific hydroclimate over the last 120kyr: a perspective from HadCM3.

    NASA Astrophysics Data System (ADS)

    Roberts, W. H. G.; Valdes, P. J.

    2014-12-01

    The focus of the majority of studies looking into the evolving tropical pacific climate on glacial/interglacial timescales has been the role of the changing orbital forcing. While this is of course the fundamental forcing that drives changes in the climate on these time scales, without a fully interactive Earth System Model the effects that the evolving ice sheets/sea level and green house gases have on the climate will be missed. In the absence of such models these other forcings must be imposed. While the impact on the temperature in both the high latitudes, and to some extent in the tropics, of all of the forcings is reasonably clear, their impact on the hydroclimate is less obvious. In this study we shall investigate what role all of the different forcings that vary over a glacial/interglacial cycle play on the hydroclimate in the eastern Tropical Pacific. We use as the basis of our study a set of three climate model experiments using the model HadCM3. Each of these simulates the last 120 thousand years as a series of time slices in one of three configurations: varying the orbital forcing; varying the orbital and greenhouse gas forcing; varying the orbital, greenhouse and ice sheet/sea level forcing. With these experiments we can deconvolve the role that each forcing plays. We will show that, in addition to the orbital forcing, both the greenhouse gas forcing and the ice sheet configuration have a large impact on the eastern Tropical Pacific's hydroclimate. Using a set of more idealised model simulations we shall elucidate the mechanisms by which each of these different forcing mechanism causes the simulated changes.

  6. Coupling of a regional atmospheric model (RegCM3) and a regional oceanic model (FVCOM) over the maritime continent

    NASA Astrophysics Data System (ADS)

    Wei, Jun; Malanotte-Rizzoli, Paola; Eltahir, Elfatih A. B.; Xue, Pengfei; Xu, Danya

    2014-09-01

    Climatological high resolution coupled climate model simulations for the maritime continent have been carried out using the regional climate model (RegCM) version 3 and the finite volume coastal ocean model (FVCOM) specifically designed to resolve regions characterized by complex geometry and bathymetry. The RegCM3 boundary forcing is provided by the EMCWF-ERA40 re-analysis. FVCOM is embedded in the Global MITgcm which provides boundary forcing. The domain of the coupled regional model covers the entire South China Sea with its through-flow, the entire Indonesian archipelago with the Indonesian through-flow (ITF) and includes a large region in the western Pacific and eastern Indian oceans. The coupled model is able to provide stable and realistic climatological simulations for a specific decade of atmospheric-oceanic variables without flux correction. The major focus of this work is on oceanic properties. First, the coupled simulation is assessed against ocean-only simulations carried out under two different sets of air-sea heat fluxes. The first set, provided by the MITgcm, is proved to be grossly deficient as the heat fluxes are evaluated by a two-dimensional, zonally averaged atmosphere and the simulated SST have anomalous cold biases. Hence the MITgcm fluxes are discarded. The second set, the NCEP re-analysis heat fluxes, produces a climatological evolution of the SST with an average cold bias of ~-0.8 °C. The coupling eliminates the cold bias and the coupled SST evolution is in excellent agreement with the analogous evolution in the SODA re-analysis data. The detailed comparison of oceanic circulation properties with the International Nusantara Stratification and Transport observations shows that the coupled simulation produces the best estimate of the total ITF transport through the Makassar strait while the transports of three ocean-only simulations are all underestimated. The annual cycle of the transport is also very well reproduced. The coupling also

  7. Dispersal of 10-14-mesh corncob granules in stacked tires.

    PubMed

    Siegel, J P; Cieslik, R; Thennisch, J; Clarke, L; Novak, R J

    1996-06-01

    Dispersal of 10-14-mesh corncob granules was evaluated in 2 random-stacked tire piles, one shingle-stacked tire pile, and one column-stacked tire pile located in a used-tire storage facility in Chicago, IL. Ninety percent and 98%, respectively, of the tires in the 2 random-stacked piles contained granules. In the shingle-stacked tire pile 87% of the tires sampled contained granules, and the number of granules per tire was dependent on depth. The 2 bottom rows of tires were 73.9% less likely to contain granules than the 5 rows above them. In the column-stacked tire pile 91.2% of the tires contained granules and the relationship between granule recovery and tire depth was logarithmic. Overall, the dispersal of 10-14-mesh corncob granules was comparable to that of 8-mesh corncob granules evaluated in a previous study at this site.

  8. Analysis of the present and future winter Pacific-North American teleconnection in the ECHAM5 global and RegCM3 regional climate models

    USGS Publications Warehouse

    Allan, Andrea M.; Hostetler, Steven W.; Alder, Jay R.

    2014-01-01

    We use the NCEP/NCAR Reanalysis (NCEP) and the MPI/ECHAM5 general circulation model to drive the RegCM3 regional climate model to assess the ability of the models to reproduce the spatiotemporal aspects of the Pacific-North American teleconnection (PNA) pattern. Composite anomalies of the NCEP-driven RegCM3 simulations for 1982–2000 indicate that the regional model is capable of accurately simulating the key features (500-hPa heights, surface temperature, and precipitation) of the positive and negative phases of the PNA with little loss of information in the downscaling process. The basic structure of the PNA is captured in both the ECHAM5 global and ECHAM5-driven RegCM3 simulations. The 1950–2000 ECHAM5 simulation displays similar temporal and spatial variability in the PNA index as that of NCEP; however, the magnitudes of the positive and negative phases are weaker than those of NCEP. The RegCM3 simulations clearly differentiate the climatology and associated anomalies of snow water equivalent and soil moisture of the positive and negative PNA phases. In the RegCM3 simulations of the future (2050–2100), changes in the location and extent of the Aleutian low and the continental high over North America alter the dominant flow patterns associated with positive and negative PNA modes. The future projections display a shift in the patterns of the relationship between the PNA and surface climate variables, which suggest the potential for changes in the PNA-related surface hydrology of North America.

  9. Impact of resolution on regional climate modeling in the source region of Yellow River with complex terrain using RegCM3

    NASA Astrophysics Data System (ADS)

    Hui, Pinhong; Tang, Jianping; Wang, Shuyu; Wu, Jian; Niu, Xiaorui; Kang, Yue

    2016-07-01

    This paper presents results from a 20-year (1990-2009) simulation by RegCM3 with both 45- and 15-km horizontal resolutions. The research focuses on the source region of Yellow River and its surrounding area, which is located on the northeast edge of the Tibetan Plateau with its very complex topography. Driven by the ECMWF ERA-interim reanalysis data, RegCM3 displays reasonable ability to reproduce the spatial patterns, annual cycles, and the interannual variabilities of regional surface climate, though the model shows wet and cold bias. The model's performance is more close to observation for the source region of Yellow River than the other part of the analysis region, and the application of high resolution of 15 km demonstrates better skill with less bias for mean climate and larger correlation coefficients for interannual variability at most stations. However, the high-resolution simulation shows little advantage for reproducing the variations of precipitation and surface air temperature with altitude. The RegCM3 model also generally reproduces the probability distribution functions (PDFs) of surface climate and, consequently, the occurrence of climatic extremes and extreme indices. The simulation with high resolution again proves to be more reliable to generate climatic extremes over complex terrain of the source region of the Yellow River, related to its better representation of complex terrain and local processes.

  10. The dynamical core, physical parameterizations, and basic simulation characteristics of the atmospheric component AM3 of the GFDL global coupled model CM3

    USGS Publications Warehouse

    Donner, L.J.; Wyman, B.L.; Hemler, R.S.; Horowitz, L.W.; Ming, Y.; Zhao, M.; Golaz, J.-C.; Ginoux, P.; Lin, S.-J.; Schwarzkopf, M.D.; Austin, J.; Alaka, G.; Cooke, W.F.; Delworth, T.L.; Freidenreich, S.M.; Gordon, C.T.; Griffies, S.M.; Held, I.M.; Hurlin, W.J.; Klein, S.A.; Knutson, T.R.; Langenhorst, A.R.; Lee, H.-C.; Lin, Y.; Magi, B.I.; Malyshev, S.L.; Milly, P.C.D.; Naik, V.; Nath, M.J.; Pincus, R.; Ploshay, J.J.; Ramaswamy, V.; Seman, C.J.; Shevliakova, E.; Sirutis, J.J.; Stern, W.F.; Stouffer, R.J.; Wilson, R.J.; Winton, M.; Wittenberg, A.T.; Zeng, F.

    2011-01-01

    The Geophysical Fluid Dynamics Laboratory (GFDL) has developed a coupled general circulation model (CM3) for the atmosphere, oceans, land, and sea ice. The goal of CM3 is to address emerging issues in climate change, including aerosol-cloud interactions, chemistry-climate interactions, and coupling between the troposphere and stratosphere. The model is also designed to serve as the physical system component of earth system models and models for decadal prediction in the near-term future-for example, through improved simulations in tropical land precipitation relative to earlier-generation GFDL models. This paper describes the dynamical core, physical parameterizations, and basic simulation characteristics of the atmospheric component (AM3) of this model. Relative to GFDL AM2, AM3 includes new treatments of deep and shallow cumulus convection, cloud droplet activation by aerosols, subgrid variability of stratiform vertical velocities for droplet activation, and atmospheric chemistry driven by emissions with advective, convective, and turbulent transport. AM3 employs a cubed-sphere implementation of a finite-volume dynamical core and is coupled to LM3, a new land model with ecosystem dynamics and hydrology. Its horizontal resolution is approximately 200 km, and its vertical resolution ranges approximately from 70 m near the earth's surface to 1 to 1.5 km near the tropopause and 3 to 4 km in much of the stratosphere. Most basic circulation features in AM3 are simulated as realistically, or more so, as in AM2. In particular, dry biases have been reduced over South America. In coupled mode, the simulation of Arctic sea ice concentration has improved. AM3 aerosol optical depths, scattering properties, and surface clear-sky downward shortwave radiation are more realistic than in AM2. The simulation of marine stratocumulus decks remains problematic, as in AM2. The most intense 0.2% of precipitation rates occur less frequently in AM3 than observed. The last two decades of

  11. Newly Installed S-1 Truss

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Launched October 7, 2002 aboard the Space Shuttle Orbiter Atlantis, the STS-112 mission lasted 11 days and performed three sessions of Extra Vehicular Activity (EVA). Its primary mission was to install the Starboard (S1) Integrated Truss Structure and Equipment Translation Aid (CETA) Cart to the International Space Station (ISS). The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss, attached to the S0 (S Zero) truss installed by the previous STS-110 mission, flows 637 pounds of anhydrous ammonia through three heat rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA is the first of two human-powered carts that will ride along the International Space Station's railway providing a mobile work platform for future extravehicular activities by astronauts. This is a view of the newly installed S1 Truss as photographed during the mission's first scheduled EVA. The Station's Canadarm2 is in the foreground. Visible are astronauts Piers J. Sellers (lower left) and David A. Wolf (upper right), both STS-112 mission specialists.

  12. Climate Impact on South America due to Land Use Degradation of Amazon Rainforest during Winter and Summer Periods by RegCM3 Model

    NASA Astrophysics Data System (ADS)

    Silva, M. E. S.; Da Rocha, R.; Pereira, G.

    2015-12-01

    In this study we investigated the climatic impact over South America region due to the increasing of deforestation at the eastern and southern regions of Amazon through the use of the climate model RegCM3 with 50 km of spatial resolution. Many studies, among global and regional models have been used to simulate climatic impact due to deforestation. Most of them used relatively coarse resolution, small domains over South America, besides do not consider deforestation as usually observed. In order to verify the RegCM3 ability to simulate climate impacts due to Amazon deforestation including relatively higher horizontal resolutions, 50 km, a larger domain, the whole South America, deforested areas more similar to the route-shaped commonly seen, and a landuse updating, the model was run for the 2001-2006 period. As the major part of the previous studies focusing Amazon deforestation, RegCM3-50km simulated over degraded areas air temperature increase, ranging from 1.0 to 2.5oC, and precipitation decreasing, ~10%. These aspects are mainly resulting from soil water depletion and roughness vegetation decreasing, both inhibiting evapotranspiration processes. Apart from these results, the model with 50 km simulated precipitation increasing, ~10%, over the eastern South America and adjacent South Atlantic ocean, after Amazon deforestation. Seeking for physical related reasons able to provide the precipitation increasing during rainy seasons, over eastern South America, we found out that upper levels high pressure system (the Bolivian High) intensification, coupled to the southeastward trough, what follows the low troposphere warming, seems to contribute to the precipitation increasing. The climatic impact simulated for winter seasons presents strongest values for areas with altered landuse, over the north region of South America.

  13. American Fisheries Society 136th Annual Meeting Lake Placid, NY 10-14 September, 2006

    USGS Publications Warehouse

    Einhouse, D.; Walsh, M.G.; Keeler, S.; Long, J.M.

    2005-01-01

    The New York Chapter of the American Fisheries Society and the New York State Department of Environmental Conservation invite you to experience the beauty of New York's famous Adirondack Park as the American Fisheries Society (AFS) convenes its 136th Annual Meeting in the legendary Olympic Village of Lake Placid, NY, 10-14 September 2006. Our meeting theme "Fish in the Balance" will explore the interrelation between fish, aquatic habitats, and man, highlighting the challenges facing aquatic resource professionals and the methods that have been employed to resolve conflicts between those that use or have an interest in our aquatic resources. As fragile as it is beautiful, the Adirondack Region is the perfect location to explore this theme. Bordered by Mirror Lake and its namesake, Lake Placid, the Village of Lake Placid has small town charm, but all of the conveniences that a big city would provide. Whether its reliving the magic of the 1980 hockey team's "Miracle on Ice" at the Lake Placid Olympic Center, getting a panoramic view of the Adirondack high peaks from the top of the 90 meter ski jumps, fishing or kayaking in adjacent Mirror Lake, hiking a mountain trail, or enjoying a quiet dinner or shopping excursion in the various shops and restaurants that line Main Street, Lake Placid has something for everyone.

  14. Tuning The Sea-Ice Seasonal Cycle Of HadCM3: Can It Reproduce Observed Trends In Sea-Ice?

    NASA Astrophysics Data System (ADS)

    Tett, S. F.; Roach, L.; Rae, C.; Cartis, C.; Mineter, M.; Steig, E. J.; Yamazaki, K.; Schurer, A. P.

    2015-12-01

    Since high quality satellite observations of sea-ice begin in 1979 Artic sea-ice extent has declined . Observed losses in Arctic sea-ice during September are greater than the majority of models in the CMIP5 archive and the multi-model average. In contrast Antarctic sea-ice has increased in contrast to an expected decline. We have carried out a set of perturbations to the HadCM3 model in which we changed the maximum ice area (a proxy for ice leads), albedo parameterizations, ice thermal conductivity and ocean diffusion. Changes in these parameters affected ice extent in both the Arctic and Antarctic. We used these simulations to identify four parameters that had most impact on minimum and maximum sea-ice extent in both hemispheres. To tune the model we used a Gauss-Newton algorithm to adjust those four parameters to minimize differences between simulated and observed sea-ice extents. With this new parameter set we then simulated the period 1940 to 2015 and compared with the default configuration of HadCM3. Compared to the default configuration the perturbed model had greater summer sea-loss in the Arctic and is consistent with observed loss estimates. However, in the Antarctic neither the perturbed or default simulations show an increase in sea-ice extent. This is in contrast to the observations which do show an increase in sea-ice extent.

  15. Coffee Beverage Quality Assessment Based on ETA/CPTEC-HadCM3 Model (A1B-IPCC/SRES Scenario), Southeastern Brazil

    NASA Astrophysics Data System (ADS)

    Giarolla, A.; Resende, N.; Chou, S. C.; Tavares, P. S.; Rodrigues, D. C.

    2012-04-01

    Environmental factors influence the coffee beverage quality and air temperature has a significant importance in this process. The grain maturation occurs very quickly in regions that present high temperatures and sometimes there is not enough time to complete all this phase adequately. In the other hand, with mild temperatures, the grain maturation occurs more slowly and it promotes a better quality beverage. The aim of this study was to assess the coffee beverage quality in the southeastern Brazil, based on climate projections using the Eta-CPTEC regional model driven by four members of an ensemble of the Met Office Hadley Centre Global Coupled climate model (HadCM3). The global model ensemble was run over the 21st century according to IPCC SRES, A1B emissions scenario. Each ensemble member presented different climate sensitivity in the analysis. The Eta-CPTEC-HadCM3 model was configured with a 40-km grid size and was run over the period of 1961-90 to represent a baseline climate, and over the period of 2011-2100 to simulate possible future changes and the effects on the coffee beverage quality. A coffee beverage quality classification, which depends on the annual air temperature proposed by Bressani (2007) and also, a quality coffee beverage sensory classification, based on Camargo and Cortez (1998) were considered in this study. An evaluation of the systematic errors (BIAS) for each member for the period from 1961 to 1990 was made. The results presented by Eta/CPTEC-HadCM3 model indicated that in the case of an occurrence of A1B emission scenario, the coffee beverage quality could be affected in this region due to the fact that the flavor may become stronger and unpleasant caused by rising air temperatures. The BIAS evaluation and subsequent errors removal demonstrated improvement in the scenarios simulations. A short review concerning agronomic techniques to mitigate extreme meteorological events or global warming on coffee crop based on Camargo (2010) also is

  16. Accurate quantum chemical modelling of the separation of Eu(3+) from Am(3+)/Cm(3+) by liquid-liquid extraction with Cyanex272.

    PubMed

    Cao, Xiaoyan; Zhang, Jun; Weissmann, Daniel; Dolg, Michael; Chen, Xuebo

    2015-08-28

    The experimentally observed extraction complexes of trivalent lanthanide Eu(3+) and actinide Am(3+)/Cm(3+) cations with Cyanex272 [bis(2,4,4-trimethylpentyl) phosphinic acid, denoted as HC272] and Cyanex301 [bis(2,4,4-trimethylpentyl) dithiophosphinic acid, denoted as HC301] have been studied by using relativistic energy-consistent 4f- and 5f-in-core pseudopotentials for trivalent f elements, combined with density functional theory and a continuum solvation model. It has been found that, as a result of hydrogen bonding, HC272 exists primarily as a self-associated species, whereas HC301 is preferably a monomer. The calculations show that in case of all three M(3+) (M = Eu, Am, Cm) ions for HC272 the extraction complexes M[H(C272)2]3 are formed prior to M(C272)3, whereas for HC301 the extraction complexes M(C301)3 have priority over M[H(C301)2]3. The calculated M-O and M-S bond lengths and the M-P distances of these preferred extraction complexes agree very well with the available experimental data. The obtained changes of the Gibbs free energies in the liquid-liquid extraction reactions (1): Maqu(3+) + 3(HC272)2,org→ M[H(C272)2]3,org + 3Haqu(+) and (2): Maqu(3+) + 3HC301org→ M(C301)3,org + 3Haqu(+) agree with the experimentally observed thermodynamical priorities of HC272 and HC301, i.e., HC272 prefers Eu(3+) over Am(3+)/Cm(3+) and HC301 prefers Am(3+)/Cm(3+) over Eu(3+). The obtained changes of the Gibbs free energies in reaction (2) (Eu, 68.1 kJ mol(-1); Am, 46.5 kJ mol(-1)) agree quite well with the experimental findings (Eu, 63.3 kJ mol(-1); Am, 44.1 kJ mol(-1)).

  17. Parameter Tuning and Calibration of RegCM3 with MIT-Emanuel Cumulus Parameterization Scheme over CORDEX East Asian Domain

    SciTech Connect

    Zou, Liwei; Qian, Yun; Zhou, Tianjun; Yang, Ben

    2014-10-01

    In this study, we calibrated the performance of regional climate model RegCM3 with Massachusetts Institute of Technology (MIT)-Emanuel cumulus parameterization scheme over CORDEX East Asia domain by tuning the selected seven parameters through multiple very fast simulated annealing (MVFSA) sampling method. The seven parameters were selected based on previous studies, which customized the RegCM3 with MIT-Emanuel scheme through three different ways by using the sensitivity experiments. The responses of model results to the seven parameters were investigated. Since the monthly total rainfall is constrained, the simulated spatial pattern of rainfall and the probability density function (PDF) distribution of daily rainfall rates are significantly improved in the optimal simulation. Sensitivity analysis suggest that the parameter “relative humidity criteria” (RH), which has not been considered in the default simulation, has the largest effect on the model results. The responses of total rainfall over different regions to RH were examined. Positive responses of total rainfall to RH are found over northern equatorial western Pacific, which are contributed by the positive responses of explicit rainfall. Followed by an increase of RH, the increases of the low-level convergence and the associated increases in cloud water favor the increase of the explicit rainfall. The identified optimal parameters constrained by the total rainfall have positive effects on the low-level circulation and the surface air temperature. Furthermore, the optimized parameters based on the extreme case are suitable for a normal case and the model’s new version with mixed convection scheme.

  18. Simulation of the GeoMIP G1 and G2 experiments with a perturbed parameter ensemble of HadCM3

    NASA Astrophysics Data System (ADS)

    Irvine, P. J.; Ridgwell, A. J.; Lunt, D. J.

    2012-12-01

    The geoengineering model intercomparison project is an attempt to assess the uncertainties in the effectiveness and climate impacts of solar radiation management (SRM) geoengineering using a multi-model ensemble (MME) of Global Circulation Models (GCM). Another approach for assessing GCM uncertainty is to use a perturbed parameter ensemble (PPE) generated from a single GCM. Although the PPE approach is limited in that all the members of the ensemble have many similarities it is still a useful way to explore uncertainty in GCM results. We simulate the G1 and G2 using a 27 member PPE of a fully-coupled CMIP3-era GCM, HadCM3, without using flux adjustments. The PPE we use is described in an article that has been submitted to the geoscientific model development journal. An analysis of the mean and spread of the PPE is made and comparisons are made with the geoMIP MME results. This comparison will support the geoMIP effort to identify the robust, and the uncertain, aspects of the simulated climate response to SRM geoengineering. This work will be complementary to the main GeoMIP MME approach and will test the utility of using PPEs of earlier generation GCMs alongside latest generation models.

  19. IUTAM Symposium on Vortex Dynamics: Formation, Structure and Function, 10-14 March 2013, Fukuoka, Japan

    NASA Astrophysics Data System (ADS)

    Fukumoto, Yasuhide

    2014-06-01

    This special issue of Fluid Dynamics Research contains the first of a two-part publication of the papers presented at the IUTAM Symposium on Vortex Dynamics: Formation, Structure and Function, held at the Centennial Hall, Kyushu University School of Medicine, Fukuoka, Japan, during the week of 10-14 March 2013. Vortices are ubiquitous structures in fluid mechanics spanning the range of scales from nanofluidics and microfluidics to geophysical and astrophysical flows. Vortices are the key to understanding many different phenomena. As a result, the subject of vortex dynamics continues to evolve and to constantly find new applications in biology, biotechnology, industrial and environmental problems. Vortices can be created by the separation of a flow from the surface of a body or at a density interface, and evolve into coherent structures. Once formed, a vortex acquires a function, depending on its individual structure. In this way, for example, insects gain lift and fish gain thrust. Surprisingly, despite the long history of vortex dynamics, only recently has knowledge about formation, structure and function of vortices been combined to yield new perspectives in the subject, thereby helping to solve outstanding problems brought about by modern advances in computer technology and improved experimental techniques. This symposium is a continuation, five years on, of the IUTAM Symposium '50 Years of Vortex Dynamics', Lyngby, Denmark that took place between 12-16 October 2008, organized by the late Professor Hassan Aref. Originally, Professor Aref was a member of the International Scientific Committee of this symposium and offered his enthusiasm and great expertise, to support its organization. To our shock, he suddenly passed away on 9 September 2011. Furthermore, Professor Slava Meleshko, a leading scientist of fluid and solid mechanics and an intimate friend of Professor Aref, was expected to make an eminent contribution to the symposium. Soon after this sad loss

  20. Investigating the Feedbacks between Land Surface Cover and North Atlantic Climate Variability in the HadCM3 Coupled Climate Model

    NASA Astrophysics Data System (ADS)

    Armstrong, E.; Valdes, P.; House, J.; Singarayer, J. S.

    2015-12-01

    The North Atlantic displays a number of major modes of decadal variability, namely the North Atlantic Oscillation (NAO) and the Atlantic Meridional Overturning Circulation (AMOC). On decadal to multi-decadal timescales, this unforced climate variability is expected to be more influential on the overall pattern of climate than anthropogenic forcing. Greater understanding of this decadal-scale variability is essential to improve its predictability, which in turn is vital to constrain uncertainty in decadal to centennial climate change predictions. Numerous studies have investigated how oceanic and atmospheric forcing modulates climate variability. However the feedbacks between the land surface and decadal variability have not been examined to the same degree. The land surface influences climate via biogeophysical and biogeochemical processes which interact and vary across a wide range of spatial and temporal scales. Increasing concentrations of CO2 are expected to drive a change in the distribution and physiology (i.e. stomatal conductance and leaf area index) of vegetation, which can alter land surface structure and influence biogeophysical processes. It is important to more accurately constrain if/how land surface cover influences decadal variability and the associated feedback mechanisms and how these may change in a warming climate. This sensitivity study will use the HadCM3 climate model to investigate the impact of a range of vegetation distributions on the strength and variability of the AMOC/NAO at increasing CO2 concentrations. We aim to elucidate feedbacks between the land surface, ocean and atmosphere in a coupled climate model and potential implications for decadal modelling studies.

  1. Sensitivity studies of high-resolution RegCM3 simulations of precipitation over the European Alps: the effect of lateral boundary conditions and domain size

    NASA Astrophysics Data System (ADS)

    Nadeem, Imran; Formayer, Herbert

    2016-11-01

    A suite of high-resolution (10 km) simulations were performed with the International Centre for Theoretical Physics (ICTP) Regional Climate Model (RegCM3) to study the effect of various lateral boundary conditions (LBCs), domain size, and intermediate domains on simulated precipitation over the Great Alpine Region. The boundary conditions used were ECMWF ERA-Interim Reanalysis with grid spacing 0.75∘, the ECMWF ERA-40 Reanalysis with grid spacing 1.125 and 2.5∘, and finally the 2.5∘ NCEP/DOE AMIP-II Reanalysis. The model was run in one-way nesting mode with direct nesting of the high-resolution RCM (horizontal grid spacing Δx = 10 km) with driving reanalysis, with one intermediate resolution nest (Δx = 30 km) between high-resolution RCM and reanalysis forcings, and also with two intermediate resolution nests (Δx = 90 km and Δx = 30 km) for simulations forced with LBC of resolution 2.5∘. Additionally, the impact of domain size was investigated. The results of multiple simulations were evaluated using different analysis techniques, e.g., Taylor diagram and a newly defined useful statistical parameter, called Skill-Score, for evaluation of daily precipitation simulated by the model. It has been found that domain size has the major impact on the results, while different resolution and versions of LBCs, e.g., 1.125∘ ERA40 and 0.7∘ ERA-Interim, do not produce significantly different results. It is also noticed that direct nesting with reasonable domain size, seems to be the most adequate method for reproducing precipitation over complex terrain, while introducing intermediate resolution nests seems to deteriorate the results.

  2. Present-day climatology and projected changes of warm and cold days in the CNRM-CM3 global climate model

    NASA Astrophysics Data System (ADS)

    Ballester, J.; Douville, H.; Chauvin, F.

    2009-01-01

    The impact of global warming on the warmest and coldest days of the annual cycle is explored according to an A2 scenario simulated by the CNRM-CM3 climate model in the framework of the IPCC AR4 intercomparison. Given the multi-model spread in IPCC projections, a validation strategy is proposed using the NCEP/NCAR reanalysis. Validation of the late twentieth century model climatology shows that warm and cold model events are slightly too long and infrequent. Although interannual trends in the warm (cold) day occurrence were positive (negative) only for six (three) of the nine considered sub-continental regions, simulated model trends are always positive (negative). This different behaviour suggests that simulated non-anthropogenic decadal variability is small relative to anthropogenic trends. Large-scale synoptic processes associated with European regional warm and cold peaks are also described and validated. Regional cold peaks are better reproduced than warm peaks, whose intensity accuracy is limited by other physical variables. Positive (negative) winter anomalies of sea and land surface temperature lead to summers with severe (weak) temperatures. These inter-annual anomalies are generated by a persistent pressure dipole over Europe. Regarding climate change, warm (cold) events will become more (less) frequent and longer (shorter). The number of warm days will largely rise and the number of cold days will dramatically decrease. The intensity of warm days will be particularly pronounced over Europe, given the projected summer drying in this region. However, according to the limited skill of the CNRM model, these results must be considered with caution.

  3. Sodium chloride in supercritical water as a function of density: potentials of mean force and an equation for the dissociation constant from 723 to 1073 K and from 0 to 0.9 g/cm(3).

    PubMed

    Liu, Wenbin; Wood, Robert H; Doren, Douglas J

    2008-06-19

    The potential of mean force (PMF) of sodium chloride in water has been calculated by using the ab initio classical free-energy perturbation method at five state points: at 973 K with densities of 0.2796, 0.0935, and 0.0101 g/cm (3) and at 723 K with densities of 0.0897 and 0.0098 g/cm (3). The method is based on a QM-MM model in which Na-H 2O, Cl-H 2O, and Na-Cl interactions are calculated by ab initio methods. The water-water interactions are from the polarizable TIP4P-FQ model. The logarithm of the dissociation constant (log K c) has been calculated from the PMF. These predictions, together with experimental measurements, were used to derive an equation for log K c at densities from 0 to 0.9 g/cm (3) and temperatures from 723 to 1073 K, as well as from 600 to 1073 K for densities from 0.29 g/cm (3) to 0.9 g/cm (3). Extrapolation of the present equation below 723 K for densities less than 0.29 g/cm (3) does not fit the experimental results. This is attributed to long-range changes in the local dielectric constant due to the high compressibility. Comparisons with previous predictions and simulations are presented.

  4. S1P control of endothelial integrity.

    PubMed

    Xiong, Yuquan; Hla, Timothy

    2014-01-01

    Sphingosine 1-phosphate (S1P), a lipid mediator produced by sphingolipid metabolism, promotes endothelial cell spreading, vascular maturation/stabilization, and barrier function. S1P is present at high concentrations in the circulatory system, whereas in tissues its levels are low. This so-called vascular S1P gradient is essential for S1P to regulate much physiological and pathophysiological progress such as the modulation of vascular permeability. Cellular sources of S1P in blood has only recently begun to be identified. In this review, we summarize the current understanding of S1P in regulating vascular integrity. In particular, we discuss the recent discovery of the endothelium-protective functions of HDL-bound S1P which is chaperoned by apolipoprotein M.

  5. CYP2S1: A short review

    SciTech Connect

    Saarikoski, Sirkku T. . E-mail: sirkku.saarikoski@ktl.fi; Rivera, Steven P.; Hankinson, Oliver; Husgafvel-Pursiainen, Kirsti

    2005-09-01

    A new member of the cytochrome P450 superfamily, CYP2S1, has recently been identified in human and mouse. In this paper, we review the data currently available for CYP2S1. The human CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. These genes also show the highest homology to the human CYP2S1. The gene has recently been found to harbor genetic polymorphism. CYP2S1 is inducible by dioxin, the induction being mediated by the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in a manner typical for CYP1 family members. In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene. This points to the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is expressed in epithelial cells of a wide variety of extrahepatic tissues. The highest expression levels have been observed in the epithelial tissues frequently exposed to xenobiotics, e.g., the respiratory, gastrointestinal, and urinary tracts, and in the skin. The observed ubiquitous tissue distribution, as well as the expression of CYP2S1 throughout embryogenesis suggest that CYP2S1 is likely to metabolize important endogenous substrates; thus far, retinoic acid has been identified. In conclusion, CYP2S1 exhibits many features of interest for human health and thus warrants further investigation.

  6. Safety assessment for the S-1 Spheromak

    SciTech Connect

    Ellis, R. Jr.; Stencel, J.R.

    1984-02-01

    The S-1 machine is part of the Magnetic Fusion Program. The goal of the Magnetic Fusion Program is to develop and demonstrate the practical application of fusion. S-1 is an experimental device which will provide an essential link in the research effort aiming at the realization of fusion power.

  7. Wackenhut Services, Incorporated: Report from the DOE Voluntary Protection Program onsite review, August 10--14, 1998

    SciTech Connect

    1999-05-01

    This report summarizes the Department of Energy Voluntary Protection Program (DOE-VPP) Review Team`s findings from the five-day onsite evaluation of Wackenhut Services, Inc. (WSI) at Savannah River Site (SRS), conducted August 10-14, 1998. The site was evaluated against the program requirements contained in US Department of Energy Voluntary Protection Program, Part 1: Program Elements to determine its success in implementing the five DOE-VPP tenets. The Team determined that WSI has met in varying degrees, all the tenets of the DOE-VPP. In every case, WSI programs and procedures exceed the level or degree necessary for compliance with existing standards, DOE Orders, and guidelines. In addition, WSI has systematically integrated their occupational safety and health (OSH) program into management and work practices at all levels. WSI`s efforts toward implementing the five major DOE-VPP tenets are summarized.

  8. The small peptide OGP(10-14) reduces proliferation and induces differentiation of TPO-primed M07-e cells through RhoA/TGFβ1/SFK pathway

    PubMed Central

    Battolla, Barbara; Bernardini, Nunzia; Petrini, Mario; Mattii, Letizia

    2011-01-01

    Summary Background Osteogenic growth peptide (OGP) is a 14-mer peptide found in relevant concentration in blood, and its carboxy-terminal fragment [OGP(10-14)] represents the active portion of the full-length peptide. In addition to stimulating bone formation, OGP(10-14) shows hematological activity. In fact, it highly enhances hematopoiesis-affecting stem progenitors. Moreover, OGP(10-14) reduces the growth and induces the differentiation of the hematological tumour cell line trombophoietin(TPO)-primed M07-e by interfering with RhoA and Src kinase pathways. In the present report, we went deeper into this mechanism and evaluated the possible interference of the OGP(10-14) signal pathway with TGFβ1 and TPO receptor Mpl. Material/Methods In OGP(10-14)-treated M07-e cells cultured with or without RhoA and Src kinases inhibitors (C3 and PP2), expression of TGFβ1, Mpl, and Src kinases was analyzed by immunoperoxidase technique. Activated RhoA expression was studied using the G-LISA™ quantitative test. Results In M07-e cells, both OGP(10-14) and PP2 activate RhoA, inhibit Src kinases, reduce Mpl expression and increase TGFβ1 expression. OGP(10-14) and PP2 show the same behavior, causing an additive effect when associated. Conclusions OGP(10-14) induces TPO-primed M07-e cells differentiation through RhoA/TGFβ1/SFKs signalling pathway. In particular OGP(10-14) acts as a Src inhibitor, showing the same effects of PP2. PMID:21169922

  9. Laboratory-Scale Column Testing Using IONSIV IE-911 for Removing Cesium from Acidic Tank Waste Simulant. 2: Determination of Cesium Exchange Capacity and Effective Mass Transfer Coefficient from a 500-cm3 Column Experiement

    SciTech Connect

    T.J. Tranter; R.D. Tillotson; T.A. Todd

    2005-04-01

    A semi-scale column test was performed using a commercial form of crystalline silicotitanate (CST) for removing radio-cesium from a surrogate acidic tank solution, which represents liquid waste stored at the Idaho National Engineering and Environmental Laboratory (INEEL). The engineered form of CST ion exchanger, known as IONSIVtmIE-911 (UOP, Mt. Laurel,NJ, USA), was tested in a 500-cm3 column to obtain a cesium breakthrough curve. The cesium exchange capacity of this column matched that obtained from previous testing with a 15-mc3 column. A numerical algorithm using implicit finite difference approximations was developed to solve the governing mass transport equations for the CST columns. An effective mass transfer coefficient was derived from solving these equations for previously reported 15 cm3 tests. The effective mass transfer coefficient was then used to predict the cesium breakthrough curve for the 500-cm3 column and compared to the experimental data reported in this paper. The calculated breakthrough curve showed excellent agreement with the data from the 500-cm3 column even though the interstitial velocity was a factor of two greater. Thus, this approach should provide a reasonable method for scale up to larger columns for treating actual tank waste.

  10. The Global S$_1$ Ocean Tide

    NASA Technical Reports Server (NTRS)

    Ray, Richard D.; Egbert, G. D.

    2003-01-01

    The small S$_1$ ocean tide is caused primarily by diurnal atmospheric pressure loading. Its excitation is therefore unlike any other diurnal tide. The global character of $S-1$ is here determined by numerical modeling and by analysis of Topex/Poseidon satellite altimeter data. The two approaches yield reasonably consistent results, and large ( $ greater than $l\\cm) amplitudes in several regions are further confirmed by comparison with coastal tide gauges. Notwithstanding their excitation differences, S$-1$ and other diurnal tides are found to share several common features, such as relatively large amplitudes in the Arabian Sea, the Sea of Okhotsk, and the Gulf of Alaska. The most noticeable difference is the lack of an S$-1$ Antarctic Kelvin wave. These similarities and differences can be explained in terms of the coherences between near-diurnal oceanic normal modes and the underlying tidal forcings. While gravitational diurnal tidal forces excite primarily a 28-hour Antarctic-Pacific mode, the S$_1$ air tide excites several other near-diurnal modes, none of which has large amplitudes near Antarctica.

  11. Clustering of breakpoints on chromosome 10 in acute T-cell leukemias with the t(10; 14) chromosome translocation

    SciTech Connect

    Kagan, J.; Finger, L.R.; Letofsky, J.; Finan, J.; Nowell, P.C.; Croce, C.M. )

    1989-06-01

    The T-cell receptor (TCR){alpha}/{delta} chain locus on chromosome 14q11 is nonrandomly involved in translocations and inversions in human T-cell neoplasms. The authors have analyzed three acute T-lymphoblastic leukemia samples carrying a t(10;14)(q24;q11) chromosome translocation by means of somatic cell hybrids and molecular cloning. In all cases studied the translocation splits the TCR {delta} chain locus. Somatic cell hybrids containing the human 10q+ chromosome resulting from the translocation retain the human terminal deoxynucleotidyltransferase gene mapped at 10q23-q24 and the diversity and joining, D{sub {delta}}2-J{sub {delta}}1, regions of the TCR {delta} chain, but not the V{sub {alpha}} region (variable region of the TCR {alpha} chain), demonstrating that the split occurred within the V{sub {alpha}}-D{sub {delta}}2 region. Molecular cloning of the breakpoint junctions revealed that the TCR {delta} chain sequences involved are made from the D{sub {delta}}2 segment. The chromosome breakpoints are clustered within a region of {approx} 263 base pairs of chromosome 10. The results suggest that the translocation of the TCR {delta} chain locus to a locus on 10q, which the authors have designated TCL3, results in deregulation of this putative oncogene, leading to acute T-cell leukemia.

  12. Defective transient endogenous spleen colony formation in S1/S1d mice.

    PubMed

    Wiktor-Jedrzejczak, W; Ahmed, A; Sharkis, S J; McKee, A; Sell, K W

    1979-04-01

    WCB6F1 mice of the genotype S1/S1d did not form transient 5-day endogenous spleen colonies following midlethal irradiation, either spontaneously or in response to postirradiation bleeding. Their hematologically normal (+/+) littermates produced colonies equivalent in number and morphologic type to a normal strain (D2B6F1), as evaluated by both macroscopic and microscopic criteria. Bone marrow cells from S1/S1d mice, when transplanted into lethally irradiated +/+ mice, were able to generate equivalent numbers of transient endogenous spleen colonies (TE-CFUs), as compared to that obtained when syngeneic +/+ marrow cells were injected into lethally irradiated +/+ recipients. A defective growth of an early class of hematopoietic progenitor cells, resulting in the clinical course of the S1/S1d anemia is suggested and confirms previous reports on the microenvironmental nature of this abnormality.

  13. Solubility of chlorargyrite (AgCl(cr./l.)) in water: New experimental data and a predictive model valid for a wide range of temperatures (273-873 K) and water densities (0.01-1 g·cm-3)

    NASA Astrophysics Data System (ADS)

    Akinfiev, Nikolay N.; Zotov, Alexander V.

    2016-04-01

    The solubility of chlorargyrite, AgCl(cr./l.), in pure water at 623, 673 and 753 (±2) K as a function of pressure in a wide range aqueous densities (0.01-0.7 g·cm-3) was determined using various experimental approaches. Combined theoretical quantum chemistry simulations of Ag speciation and structure with a recently developed equation of state (EoS) for aqueous neutral species (Akinfiev and Diamond, 2003) were applied to describe published and newly made AgCl(cr./l.) solubility measurements in water. The use of the employed EoS for AgCl(H2O)(aq) cluster is found out to provide a good description of the whole set of experimental measurements in a wide range of temperatures (273-753 K), water densities (0.01-0.7 g·cm-3), and pressures of 0.1-100 MPa. Also, the proposed AgCl(H2O)(aq) thermodynamic description is proved to be valid for a dense aqueous fluid (0.7-1 g·cm-3) at 273-623 K and saturation water pressure. Although silver obviously shows greater affinity to dense aqueous fluid, AgCl hydration in the vapour phase is demonstrated to be also significant. A model extrapolation to magmatic conditions predicts an appreciable silver content even in low density fluids, thus supporting the hypothesis of metal transport with vapour.

  14. Restless legs syndrome mimicking S1 radiculopathy.

    PubMed

    Zambelis, Th; Wolgamuth, B R; Papoutsi, S N; Economou, N T

    2016-01-01

    Α case of a chronic idiopathic form of a severe type of Restless Legs Syndrome (RLS), which developed during pregnancy and persisted after this, misdiagnosed for 34 years as radiculopathy S1, is reported. In spite of the thorough clinical and laboratory investigation, in addition to constant changes of the therapeutic approach, the diagnosis of S1 radiculopathy could not be confirmed, resulting in a chronic clinical course; the latter was characterized by relapses and remissions not attributed or linked in any way to the treatment (various types of). In fact, it was due to a routine workup in a sleep clinic, where the patient was referred because of a coincident chronic insomnia (Restless Legs Syndrome is a known and important cause of insomnia/chronic insomnia), which resulted in a proper diagnosis and treatment of this case. With the use of Restless Legs Syndrome appropriate treatment (Pramipexole 0.18 mg taken at bedtime, a dopaminergic agent and Level A recommended drug for Restless Legs Syndrome) an excellent response and immediate elimination of symptoms was achieved. Restless Legs Syndrome may present with a variety of symptoms (with the most prominent shortly being reported with the acronym URGE: Urge to move the legs usually associated with unpleasant leg sensations, Rest induces symptoms, Getting active brings relief, Evening and night deteriorate symptoms); given the fact that Restless Legs Syndrome presents with a great variety and heterogeneity of symptoms (mostly pain, dysesthesia and paresthesia), which may occur in several other diseases (the so called "RLS mimics"), proper diagnosis of Restless Legs Syndrome usually fails. Restless Legs Syndrome misinterpreted as S1 radiculopathy, to the best of our knowledge, has not been reported yet in the literature. Here, case history, clinical course and common RLS mimics are presented. Different forms of Restless Legs Syndrome manifestations, which are commonly -as in this case- misinterpreted due to their

  15. Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

    PubMed

    Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

    2014-07-01

    The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates.

  16. The functional roles of S1P in immunity.

    PubMed

    Hisano, Yu; Nishi, Tsuyoshi; Kawahara, Atsuo

    2012-10-01

    The lipid mediator sphingosine-1-phosphate (S1P) is generated within cells from sphingosine by two sphingosine kinases (SPHK1 and SPHK2). Intracellularly synthesized S1P is released into the extracellular fluid by S1P transporters, including SPNS2. Released S1P binds specifically to the G protein-coupled S1P receptors (S1PR1/S1P(1)-S1PR5/S1P(5)), which activate a diverse range of downstream signalling pathways. Recent studies have proposed that one of the central physiological functions of intercellular S1P signalling is in lymphocyte trafficking in vivo because genetic disruption of SPHK1/2, SPNS2 or S1PR1/S1P(1) in mice induces a lymphopenia phenotype. In this review, we discuss the current understanding of intercellular S1P signalling in the context of immunity.

  17. Nonfatal and Fatal Self-Harm Injuries among Children Aged 10-14 Years--United States and Oregon, 2001-2003

    ERIC Educational Resources Information Center

    Vajani, Madhavi; Annest, Joseph L.; Crosby, Alex E.; Alexander, Janice D.; Millet, Lisa M.

    2007-01-01

    Fatal and nonfatal injuries due to suicidal behavior among younger adolescents are of growing concern for many communities. We examined the incidence and patterns of these injuries among persons aged 10-14 years using three databases, two national and a third from Oregon. Suffocation and firearm gunshot were the leading external causes of suicide;…

  18. Absolute configuration of sex pheromone for tea tussock moth,Euproctis pseudoconspersa (strand)via synthesis of (R)- and (S)-10, 14-dimethyl-1-pentadecyl isobutyrates.

    PubMed

    Ichikawa, A; Yasuda, T; Wakamura, S

    1995-05-01

    (R)- and (S)-10,14-dimethyl-1-pentadecyl isobutyrates were synthesized from (S)- and (R)-citronellols, respectively. TheR enantiomer was as active as the natural pheromone but theS enantiomer was less active in the electrophysiological analyses, which provided conclusive proof that the absolute configuration of the natural pheromone isR.

  19. Studying the properties and response of a large volume (946 cm3) LaBr3:Ce detector with γ-rays up to 22.5 MeV

    NASA Astrophysics Data System (ADS)

    Mazumdar, I.; Gothe, D. A.; Anil Kumar, G.; Yadav, N.; Chavan, P. B.; Patel, S. M.

    2013-03-01

    This paper presents the results of our measurements and detailed simulations using GEANT4 to investigate the performance of a large volume (946 cm3) cylindrical (3.5 in.diameter×6 in.length) LaBr3:Ce detector. The properties of the detector have been studied using γ-rays from radioactive sources and in-beam reaction, from few hundred keV to 22.5 MeV. The salient features, which have been studied in-depth, are the uniformity and internal activity of the crystal, the energy and timing resolutions, linearity of the response up to 22.5 MeV, and efficiencies. A highly linear response has been observed by extracting the energy signal from a lower dynode and operating the PMT at a low voltage. The detector is to be primarily used for measuring high energy γ-rays spectra from Giant Dipole Resonance (GDR) decay studies.

  20. 1015 cm-3 eV-1 level detection of density of states of a p-type polymer by hν-dependent high-sensitivity ultraviolet photoemission spectroscopy

    NASA Astrophysics Data System (ADS)

    Sato, Tomoya; Kinjo, Hiroumi; Yamazaki, Junki; Ishii, Hisao

    2017-01-01

    We propose a method, called hν-dependent high-sensitivity ultraviolet photoemission spectroscopy, to observe the density of states (DOS) in a very wide range from HOMO to extremely weak gap states (1022 to 1015 cm-3 eV-1 in density of states). The method was applied to a p-type semiconducting polymer. A series of spectra for hν = 4.4-7.7 eV were recorded, and the DOS was obtained by overlapping the spectral part with a similar line shape between adjacent photon energy spectra to eliminate the photon energy dependence of the photoionization cross section. This method can be applied to both organic and inorganic materials, providing useful information about the DOS of functional materials.

  1. Frequency measurement of the 2S(1/2)-2D(3/2) electric quadrupole transition in a single 171Yb+ ion.

    PubMed

    Webster, Stephen; Godun, Rachel; King, Steven; Huang, Guilong; Walton, Barney; Tsatourian, Veronika; Margolis, Helen; Lea, Stephen; Gill, Patrick

    2010-03-01

    We report on precision laser spectroscopy of the 2S(1/2)(F = 0)-2D(3/2) (F = 2, m(F) = 0) clock transition in a single ion of 171Yb+. The absolute value of the transition frequency, determined using an optical frequency comb referenced to a hydrogen maser, is 688358979309310 +/- 9 Hz. This corresponds to a fractional frequency uncertainty of 1.3 x 10(-14).

  2. Exit Strategies: S1P Signaling and T Cell Migration.

    PubMed

    Baeyens, Audrey; Fang, Victoria; Chen, Cynthia; Schwab, Susan R

    2015-12-01

    Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies to measure S1P.

  3. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling.

    PubMed

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  4. S1-equivariant Chern-Weil constructions on loop space

    NASA Astrophysics Data System (ADS)

    McCauley, Thomas

    2017-02-01

    We study the existence of S1-equivariant characteristic classes on certain natural infinite rank bundles over the loop space LM of a manifold M. We discuss the different S1-equivariant cohomology theories in the literature and clarify their relationships. We attempt to use S1-equivariant Chern-Weil techniques to construct S1-equivariant characteristic classes. The main result is the construction of a sequence of S1-equivariant characteristic classes on the total space of the bundles, but these classes do not descend to the base LM. Nevertheless, we conclude by identifying a class of bundles for which the S1-equivariant first Chern class does descend to LM.

  5. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    SciTech Connect

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  6. Conformationally Constrained, Stable, Triplet Ground State (S = 1) Nitroxide Diradicals. Antiferromagnetic Chains of S = 1 Diradicals

    SciTech Connect

    Rajca, Andrzej; Takahashi, Masahiro; Pink, Maren; Spagnol, Gaelle; Rajca, Suchada

    2008-06-30

    Nitroxide diradicals, in which nitroxides are annelated to m-phenylene forming tricyclic benzobisoxazine-like structures, have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and {sup 1}H NMR) spectroscopy, as well as magnetic studies in solution and in solid state. For the octamethyl derivative of benzobisoxazine nitroxide diradical, the conformationally constrained nitroxide moieties are coplanar with the m-phenylene, leading to large values of 2J (2J/k > 200 K in solution and 2J/k >> 300 K in the solid state). For the diradical, in which all ortho and para positions of the m-phenylene are sterically shielded, distortion of the nitroxide moieties from coplanarity is moderate, such that the singlet-triplet gaps remain large in both solution (2J/k > 200 K) and the solid state (2J/k {approx} 400-800 K), though an onset of thermal depopulation of the triplet ground state is detectable near room temperature. These diradicals have robust triplet ground states with strong ferromagnetic coupling and good stability at ambient conditions. Magnetic behavior of the nitroxide diradicals at low temperature is best fit to the model of one-dimensional S = 1 Heisenberg chains with intrachain antiferromagnetic coupling. The antiferromagnetic coupling between the S = 1 diradicals may be associated with the methyl nitroxide C-H {hor_ellipsis} O contacts, including nonclassical hydrogen bonds. These unprecedented organic S = 1 antiferromagnetic chains are highly isotropic, compared to those of the extensively studied Ni(II)-based chains.

  7. Laboratory-Scale Column Testing Using IONSIV IE-911 for Removing Cesium from Acidic Tank Waste Simulant. 1: Cesium Exchange Capacity of a 15-cm3 Column and Dynamic Stability of the Exchange Media

    SciTech Connect

    T.J. Tranter; R.D. Tillotson; T.A. Todd

    2005-04-01

    Bench-scale column tests were performed using a commercial form of crystalline silicotitanate (CST) for removing radio-cesium from a surrogate acidic tank solution representative of liquid waste stored at the Idaho National Engineering and Environmental Laboratory (INEEL). An engineered form of CST ion exchanger, known as IONSIVtm IE-911 (UOP, Mt Laurel, NJ, USA), was tested in 15 cm3 columns at a flow rate of 5 bed volumes per hour. These experiments showed the ion exchange material to have reasonable selectivity and capacity for removing cesium from the complex chemical matrix of the solution. However, previous testing indicated that partial neutralization of the feed stream was necessary to increase the stability of the ion exchange media. Thus, in these studies, CST degradation was determined as a function of throughput in order to better assess the stability characteristics of the exchanger for potential future waste treatment applications. Results of these tests indicate that the degradation of the CST reaches a maximum very soon after the acidic feed is introduced to the column and then rapidly declines. Total dissolution of bed material did not exceed 3% under the experimental regime used.

  8. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.

    PubMed

    Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Sorci-Thomas, Mary G; Thomas, Michael J; Lopes-Virella, Maria F; Luttrell, Louis M; Hammad, Samar M; Klein, Richard L

    2017-02-01

    HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

  9. Chemical and genetic tools to explore S1P biology.

    PubMed

    Cahalan, Stuart M

    2014-01-01

    The zwitterionic lysophospholipid Sphingosine 1-Phosphate (S1P) is a pleiotropic mediator of physiology and pathology. The synthesis, transport, and degradation of S1P are tightly regulated to ensure that S1P is present in the proper concentrations in the proper location. The binding of S1P to five G protein-coupled S1P receptors regulates many physiological systems, particularly the immune and vascular systems. Our understanding of the functions of S1P has been aided by the tractability of the system to both chemical and genetic manipulation. Chemical modulators have been generated to affect most of the known components of S1P biology, including agonists of S1P receptors and inhibitors of enzymes regulating S1P production and degradation. Genetic knockouts and manipulations have been similarly engineered to disrupt the functions of individual S1P receptors or enzymes involved in S1P metabolism. This chapter will focus on the development and utilization of these chemical and genetic tools to explore the complex biology surrounding S1P and its receptors, with particular attention paid to the in vivo findings that these tools have allowed for.

  10. 26 CFR 1.414(s)-1 - Definition of compensation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of compensation. 1.414(s)-1 Section 1.414(s)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(s)-1 Definition...

  11. Sphingosine-1-Phosphate (S1P) Lyase Inhibition Causes Increased Cardiac S1P Levels and Bradycardia in Rats.

    PubMed

    Harris, Christopher M; Mittelstadt, Scott; Banfor, Patricia; Bousquet, Peter; Duignan, David B; Gintant, Gary; Hart, Michelle; Kim, Youngjae; Segreti, Jason

    2016-10-01

    Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats.

  12. Femtosecond optical-to-microwave frequency divider with a relative instability of 10^{-14}{-} 10^{-16}(\\tau = 1 {-} 100\\ {\\text{s}})

    NASA Astrophysics Data System (ADS)

    Kireev, A. N.; Tausenev, A. V.; Tyurikov, D. A.; Shelkovnikov, A. S.; Shepelev, D. V.; Konyashchenko, A. V.; Gubin, M. A.

    2016-12-01

    We have developed a low-noise optical-to-microwave frequency divider based on a femtosecond erbium fibre laser. The source of an optical signal was a {\\text{He}} - {\\text{Ne/CH}}4 frequency standard. Comparison of two frequency dividers showed that the relative instability of output microwave signals, introduced by the dividers, is 10-14- 10-16 for the averaging time τ = 1 - 100 {\\text{s}}. The instability obtained corresponds to the requirements imposed on interrogative oscillators for time and frequency standards based on Cs or Rb atomic fountains.

  13. Targeting sphingosine 1-phosphate (S1P) levels and S1P receptor functions for therapeutic immune interventions.

    PubMed

    Gräler, Markus H

    2010-01-01

    Sphingosine 1-phosphate (S1P) is an important regulator of many different immune functions including lymphocyte circulation, antigen presentation, and T cell development. It stimulates five G protein-coupled receptors designated S1P(1-5), which are also expressed by immune cells. S1P receptors couple to different heterotrimeric G proteins including G alpha i, q, and 12/13, and elicit cellular signalling events by activating the small GTPases Rac and Rho and protein kinases Akt, ERK, and JNK, and by inducing cellular calcium flux and inhibiting cAMP accumulation, amongst others. S1P is the exit signal for lymphocytes leaving lymphoid organs and present in blood and lymph at high nanomolar concentrations due to the S1P-producing activity of sphingosine kinases (SK). The S1P-degrading enzyme S1P-lyase maintains low amounts of S1P in lymphoid organs. Disrupting this concentration difference by S1P receptor agonists and antagonists like FTY720, SEW2871, and VPC23019, by an anti-S1P antibody, or by inhibiting the S1P-lyase has therapeutic potential for autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis and for many other disorders like cancer, fibrosis, inflammation, macular degeneration, diabetic retinopathy, and glaucoma. This report aims to provide a brief overview of concepts, approaches, pharmaceutical compounds, and targets that are currently used to modulate S1P-driven immune functions.

  14. cap alpha. -chain locus of the T-cell antigen receptor is involved in the t(10; 14) chromosome translocation of T-cell acute lymphocytic leukemia

    SciTech Connect

    Kagan, J.; Finan, J.; Letofsky, J.; Besa, E.C.; Nowell, P.C.; Croce, C.M.

    1987-07-01

    Human leukemic T cells carrying a t(10;14)(q24;q11) chromosome translocation were fused with mouse leukemic T cells, and the hybrids were examined for genetic markers of human chromosomes 10 and 14. Hybrids containing the human 10q+ chromosome had the human genes for terminal deoxynucleotidyltransferase that has been mapped at 10q23-q25 and for C/sub ..cap alpha../ (the constant region of TCRA (the ..cap alpha..-chain locus of the T-cell antigen receptor gene)), but not for V/sub ..cap alpha../ (the variable region of TCRA). Hybrids containing the human 14q- chromosome retained the V/sub ..cap alpha../genes. Thus the 14q11 breakpoint in the t(10;14) chromosome translocation directly involves TCRA, splitting the locus in a region between the V/sub ..cap alpha../ and the C/sub ..cap alpha../ genes. These results suggest that the translocation of the C/sub ..cap alpha../ locus to a putative cellular protooncogene located proximal to the breakpoint at 10q24, for which the authors propose the name TCL3, results in its deregulation, leading to T-cell leukemia. Since hybrids with the 10q+ chromosome also retained the human terminal deoxynucleotidyltransferase gene, it is further concluded that the terminal deoxynucleotidyltransferase locus is proximal to the TCL3 gene, at band 10q23-q24.

  15. Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

    PubMed

    Tsai, Hsing-Chuan; Han, May H

    2016-07-01

    Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

  16. S1P and the birth of platelets.

    PubMed

    Hla, Timothy; Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

    2012-11-19

    Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P(1) receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P(1) receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12-CXCR4 axis. Pharmacologic modulation of the S1P(1) receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P(4) receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P(1) duet that could potentially be harnessed for clinical translation.

  17. Tertiary trisomy of 10p15.pter and 14pter.ql3 due to maternal translocation t(10;14)(p15;q13).

    PubMed

    Cetin, Z; Mihci, E; Keser, I; Luleci, G

    2012-01-01

    Double partial trisomy resulting from 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. We present here a first patient with multiple congenital malformations associated with double partial trisomy of 10pter-p15 and 14pter-q13 resulting from 3:1 segregation of maternal balanced translocation t(10;14)(p15;q13). Proximal partial trisomy of chromosome 14 and subterminal trisomy of the short arm of the chromosome 10 are rare. The present case is the first case with double partial trisomy of these segments resulting from 3:1 segregation of a maternal balanced translocation.

  18. Current Development of Anti-Cancer Drug S-1

    PubMed Central

    Giri, Anil; Shakya, Suraj; Shakya, Sujana; Sapkota, Binaya; Pramod, KC

    2016-01-01

    S-1 is a novel oral fluoropyrimidine derivative, widely used for treating gastric, pancreatic, lung, head, neck and breast carcinomas. It is designed to enhance the clinical utility of an oral fluoropyrimidine and is associated with low gastrointestinal toxicity. S-1 consists of three pharmacological agents (at a molar ratio of 1:0.4:1)-Tegafur (FT), a prodrug of 5-Fluorouracil (5-FU), 5-Chloro-2-4-Dihydroxypyridine (CDHP), which inhibits the activity of Dihydropyrimidine Dehydrogenase (DPD) and Oxonic Acid (Oxo), which reduces Gastrointestinal (GI) toxicity of 5-FU. The present article reviews the current development of clinical study of S-1. PMID:28050491

  19. Causes and prevalence of traumatic injuries to the permanent incisors of school children aged 10-14 years in Maseru, Lesotho.

    PubMed

    Lin, H; Naidoo, Sudeshni

    2008-04-01

    Traumatic dental injuries are widespread in the population and the prevalence of traumatic dental injuries among school children in different parts of the world varies from about 3% to 45%. Most injuries involve the anterior teeth, which may lead to eating restrictions, changes in physical appearance, speech defects and psychological impacts that affect the child's quality of life. A cross-sectional survey was carried out to investigate the prevalence, aetiology and types of injuries to permanent incisors among schoolchildren aged 10-14 years from Maseru, Lesotho. Upper and lower permanent incisors were examined for dental injuries. The prevalence of traumatic injuries to the permanent incisor teeth was 9.3% (13.3% boys and 6.3% girls). Significantly more boys than girls suffered injury. The most common type of injury was enamel fractures and most common cause was falls. Health promotion policies should aim to create an appropriate and safe environment for children. Soft playground surfaces, school-crossing patrols, marked zebra crossings and bicycle lanes would help create a safe environment. Speed limits for cars and the use of seat belts, air bags, special car seats for children and bicycle helmets should be enforced. Mouth guards should be used when playing sport, in particular contact sports. Education regarding the epidemiology of dental injuries and their prevention through health promotion may play a major role in reducing the prevalence of dental injury and avoiding the financial costs of treatment, especially in developing countries.

  20. Cosmic ray chemical composition estimated between 2 × 10 14 eV and 2 × 10 16 eV using muon size fluctuations

    NASA Astrophysics Data System (ADS)

    Mitsui, K.; Aoki, T.; Ohashi, Y.; Okada, A.; Muraki, Y.; Maehara, O.; Kojima, H.; Shibata, S.; Takahashi, T.; Kobayakawa, K.; Capdevielle, J. N.

    1995-03-01

    Accurate measurement of the total number of muons in an air shower is important for estimating the cosmic ray chemical composition. In order to translate this view into action, we have constructed an air shower array at Ohya. Many large muon detectors have been deployed in the stone mine and the total area amounts to about 400 m 2. At the ground surface, scintillation counters have been deployed for determining the shower size and arrival direction of an air shower. From the data obtained, we estimated the cosmic ray chemical composition between 2 × 10 14 eV and 2 × 10 16 eV, which includes the well known spectrum's "knee". As a method of estimation, we took the muon size fluctuation. The estimated rate of protons becomes relatively low, and that of helium nuclei increases, above an energy of 2 × 10 15 eV. Also, the fraction of very heavy nuclei such as iron increases above this energy.

  1. Associations between prolonged sedentary time and breaks in sedentary time with cardiometabolic risk in 10-14-year-old children: The HAPPY study.

    PubMed

    Bailey, Daniel P; Charman, Sarah J; Ploetz, Thomas; Savory, Louise A; Kerr, Catherine J

    2016-11-28

    This study examines the association between prolonged sedentary time and breaks in sedentary time with cardiometabolic risk in 10-14-year-old children. This cross-sectional design study analysed accelerometry-determined sedentary behaviour and physical activity collected over 7 days from 111 (66 girls) UK schoolchildren. Objective outcome measures included waist circumference, fasting lipids, fasting glucose, blood pressure, and cardiorespiratory fitness. Logistic regression was used for the main data analysis. After adjustment for confounders, the odds of having hypertriglyceridaemia (P = 0.03) and an increased clustered cardiometabolic risk score (P = 0.05) were significantly higher in children who engaged in more prolonged sedentary bouts per day. The number of breaks in sedentary time per day was not associated with any cardiometabolic risk factor, but longer mean duration of daily breaks in sedentary time were associated with a lower odds of having abdominal adiposity (P = 0.04) and elevated diastolic blood pressure (P = 0.01). These associations may be mediated by engagement in light activity. This study provides evidence that avoiding periods of prolonged uninterrupted sedentary time may be important for reducing cardiometabolic disease risk in children.

  2. 7S(1/2) ? 9S(1/2) two-photon spectroscopy of trapped francium.

    PubMed

    Simsarian, J E; Shi, W; Orozco, L A; Sprouse, G D; Zhao, W Z

    1996-12-01

    We report on the spectroscopic measurement of the (210)Fr 9S(1/2) energy obtained by two-photon excitation of atoms confined and cooled in a magneto-optic trap. The resonant intermediate level 7P(3/2) is the upper state of the trapping transition. We have measured the energy difference between the 9S(1/2) state and the 7S(1/2) ground state to be 25 671.021 +/- 0.006 cm(-1).

  3. [Evaluation of Drug Interaction between S-1 and Warfarin].

    PubMed

    Yamamoto, Kaori; Suzuki, Shinya; Ikegawa, Kiwako; Nomura, Hisanaga; Fuse, Nozomu; Saito, Shinichiro

    2016-01-01

    Prolonged prothrombin time is observed in patients taking warfarin (WF) with a fluoropyrimidine, such as S-1. When WF is combined with S-1, the prothrombin time-international normalized ratio (PT-INR) and dose adjustment of WF should be closely monitored. To date, no clinical data have been reported in terms of the relation between temporal variation of PT-INR and its therapeutic range. In this study, we retrospectively collected patients' clinical data including PT-INR. We identified 21 patients receiving WF therapy before the start of S-1 treatment. Patient characteristics were male/female: 18/3, median age: 69 (range 48-81) years old, cancer of gastric/lung/pancreatic/other: 8/5/4/4, and history of deep vein thrombosis (DVT)/atrial fibrillation (AF)/cerebral infarction (CI)/other: 11/6/2/2. The PT-INR of 16 patients exceeded normal upper limits after taking S-1 with WF. The median time to exceed the PT-INR upper therapeutic range is 25 (range 3-77) days. Patients receiving WF anticoagulant therapy concomitant with S-1 should have their PT-INR closely monitored and WF doses adjusted accordingly.

  4. The S=1 Underscreened Anderson Lattice model for Uranium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Simões, A. S. R.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing coexistence of the Kondo effect and ferromagnetic order are investigated within the degenerate Anderson Lattice Hamiltonian, describing a 5f2 electronic configuration with S = 1 spins. Through the Schrieffer-Wolff transformation, both an exchange Kondo interaction for the S = 1 f-spins and an effective f-band term are obtained, allowing to describe the coexistence of Kondo effect and ferromagnetic ordering and a weak delocalization of the 5f-electrons. We calculate the Kondo and Curie temperatures and we can account for the pressure dependence of the Curie temperature of UTe.

  5. L5 – S1 Segmental Kinematics After Facet Arthroplasty

    PubMed Central

    Voronov, Leonard I.; Havey, Robert M.; Rosler, David M.; Sjovold, Simon G.; Rogers, Susan L.; Carandang, Gerard; Ochoa, Jorge A.; Yuan, Hansen; Webb, Scott

    2009-01-01

    Background Facet arthroplasty is a motion restoring procedure. It is normally suggested as an alternative to rigid fixation after destabilizing decompression procedures in the posterior lumbar spine. While previous studies have reported successful results in reproducing normal spine kinematics after facet replacement at L4-5 and L3-4, there are no data on the viability of facet replacement at the lumbosacral joint. The anatomy of posterior elements and the resulting kinematics at L5-S1 are distinctly different from those at superior levels, making the task of facet replacement at the lumbosacral level challenging. This study evaluated the kinematics of facet replacement at L5-S1. Methods Six human cadaveric lumbar spines (L1-S1, 46.7 ± 13.0 years) were tested in the following sequence: (1) intact (L1-S1), (2) complete laminectomy and bilateral facetectomy at L5-S1, and (3) implantation of TFAS-LS (Lumbosacral Total Facet Arthroplasty System, Archus Orthopedics, Redmond, Washington) at L5-S1 using pedicle screws. Specimens were tested in flexion (8Nm), extension (6Nm), lateral bending (LB, ± 6Nm), and axial rotation (AR, ± 5Nm). The level of significance was α = .017 after Bonferroni correction for three comparisons: (1) intact vs. destabilized, (2) destabilized vs. reconstructed, and (3) intact vs. reconstructed. Results Laminectomy-facetectomy at L5-S1 increased the L5-S1 angular range of motion (ROM) in all directions. Flexion-extension (F-E) ROM increased from 15.3 ± 2.9 to 18.7 ± 3.5 degrees (P < .017), LB from 8.2 ± 1.8 to 9.3 ± 1.6 degrees (P < .017), and AR from 3.7 ± 2.0 to 5.9 ± 1.8 degrees (P < .017). The facet arthroplasty system decreased ROM compared to the laminectomy-facetectomy condition in all tested directions (P < .017). The facet arthroplasty system restored the L5-S1 ROM to its intact levels in LB and AR (P > .017). F-E ROM after the facet arthroplasty system implantation was smaller than the intact value (10.1 ± 2.2 vs. 15.3 ± 2

  6. Excitation of nutation by the global radiational S1 tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, M.; Salstein, D. A.; Einspigel, D.; Boehm, J.

    2014-12-01

    Cyclic mass redistributions in the atmosphere and oceans related to the global radiational S1 tide elicit seasonal perturbations of Earth's nutation at a level of 0.1 mas (milliarcseconds). The present study provides an up-to-date assessment of these excitation effects on the basis of 10-year surface and isobaric level data from three, previously unavailable global atmospheric reanalysis systems. We retrieve numerical values of in- and out-of-phase nutation corrections for seasonally modulated S1 variations and indicate how model improvements, specifically in terms of the representation of tidal oscillations, lead to different estimates with respect to earlier reanalyses. Motion term signals in nutation display a close agreement across all probed datasets, whereas larger disparities remain among mass term excitation estimates due to their dependency on small-scale diurnal surface pressure oscillations. A simple time-stepping model for barotropic ocean dynamics, based on the shallow water equations and driven by air pressure tide climatologies, represents an appropriate means to determine global S1 estimates of sea level heights and currents that are consistent with the respective forcing fields from each reanalysis. We address the intricacies of constructing such a model and compare our preliminary oceanic angular momentum solutions to those from more established hydrodynamic forward integrations. The combined influence of the S1 tide on Earth's nutation, associated with both atmosphere and ocean dynamics, is found to yield a rough agreement with observations from geodetic VLBI (Very Long Baseline Interferometry) measurements.

  7. SpS1-Gas in protoplanetary disks

    NASA Astrophysics Data System (ADS)

    Goto, Miwa

    2010-11-01

    High resolution infrared spectroscopy is the key technique to look at the inner regions of protoplanetary disks. As molecular hydrogen is an inefficient emitter, CO gas is the single most important molecular probe of the disk. The energy gaps of the vibrationally excited levels (ΔE > 3000 K) and the critical density required to keep the molecules in the excited state (nc ~ 1010cm-3) match well to the physical condition of the inner regions of protoplanetary disks. In order to resolve the vibrational lines of different rotational states, a spectral resolving power of λ/Δλ > 10000 is necessary; or even higher (> 30000 -100000), if we would like to fully resolve the gas kinematics. Scoville et al. (1980) provided the fundamentals of the excitation mechanisms, which is essential for the interpretation of the vibrational transitions of CO, and pioneered the study of the circumstellar environment with infrared CO lines in the observation of BN (Scoville et al. (1983)). The bandhead emission of CO at 2.3 μm from young stars was unambiguously attributed to the circumstellar disks by Carr (1989) and Najita et al. (1996), because the gas kinematics matches well to what is expected from Keplerian rotation. Since then, the gas kinematics have been extensively used to shed light on peculiar disk structures, such as the inner truncation (Brittain et al. 2003), the outer truncation (Najita et al. 2008), and the gap (van der Plas et al. 2008; though this is an oxygen forbidden line).

  8. Regulation of insulin and type 1 insulin-like growth factor signaling and action by the Grb10/14 and SH2B1/B2 adaptor proteins.

    PubMed

    Desbuquois, Bernard; Carré, Nadège; Burnol, Anne-Françoise

    2013-02-01

    The effects of insulin and type 1 insulin-like growth factor (IGF-1) on metabolism, growth and survival are mediated by their association with specific receptor tyrosine kinases, which results in both receptor and substrate phosphorylation. Phosphotyrosine residues on receptors and substrates provide docking sites for signaling proteins containing SH2 (Src homology 2) domains, including molecular adaptors. This review focuses on the regulation of insulin/IGF-1 signaling and action by two adaptor families with a similar domain organization: the growth factor receptor-bound proteins Grb7/10/14 and the SH2B proteins. Both Grb10/14 and SH2B1/B2 associate with the activation loop of insulin/IGF-1 receptors through their SH2 domains, but association of Grb10/14 also involves their unique BPS domain. Consistent with Grb14 binding as a pseudosubstrate to the kinase active site, insulin/IGF-induced activation of receptors and downstream signaling pathways in cultured cells is inhibited by Grb10/14 adaptors, but is potentiated by SH2B1/B2 adaptors. Accordingly, Grb10 and Grb14 knockout mice show improved insulin/IGF sensitivity in vivo, and, for Grb10, overgrowth and increased skeketal muscle and pancreatic β-cell mass. Conversely, SH2B1-depleted mice display insulin and IGF-1 resistance, with peripheral depletion leading to reduced adiposity and neuronal depletion leading to obesity through associated leptin resistance. Grb10/14 and SH2B1 adaptors also modulate insulin/IGF-1 action by interacting with signaling components downstream of receptors and exert several tissue-specific effects. The identification of Grb10/14 and SH2B1 as physiological regulators of insulin signaling and action, together with observations that variants at their gene loci are associated with obesity and/or insulin resistance, highlight them as potential therapeutic targets for these conditions.

  9. Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

    PubMed

    Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

    2016-01-15

    Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders.

  10. The Global S_1 Tide in Earth's Nutation

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Einšpigel, David; Salstein, David; Böhm, Johannes

    2016-05-01

    Diurnal S_1 tidal oscillations in the coupled atmosphere-ocean system induce small perturbations of Earth's prograde annual nutation, but matching geophysical model estimates of this Sun-synchronous rotation signal with the observed effect in geodetic Very Long Baseline Interferometry (VLBI) data has thus far been elusive. The present study assesses the problem from a geophysical model perspective, using four modern-day atmospheric assimilation systems and a consistently forced barotropic ocean model that dissipates its energy excess in the global abyssal ocean through a parameterized tidal conversion scheme. The use of contemporary meteorological data does, however, not guarantee accurate nutation estimates per se; two of the probed datasets produce atmosphere-ocean-driven S_1 terms that deviate by more than 30 μ as (microarcseconds) from the VLBI-observed harmonic of -16.2+i113.4 μ as. Partial deficiencies of these models in the diurnal band are also borne out by a validation of the air pressure tide against barometric in situ estimates as well as comparisons of simulated sea surface elevations with a global network of S_1 tide gauge determinations. Credence is lent to the global S_1 tide derived from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) and the operational model of the European Centre for Medium-Range Weather Forecasts (ECMWF). When averaged over a temporal range of 2004 to 2013, their nutation contributions are estimated to be -8.0+i106.0 μ as (MERRA) and -9.4+i121.8 μ as (ECMWF operational), thus being virtually equivalent with the VLBI estimate. This remarkably close agreement will likely aid forthcoming nutation theories in their unambiguous a priori account of Earth's prograde annual celestial motion.

  11. The global S1 tide and Earth's nutation

    NASA Astrophysics Data System (ADS)

    Schindelegger, M.; Böhm, J.; Salstein, D. A.

    2015-08-01

    Diurnal S1 tidal atmospheric oscillations induced by the cyclic heating of air masses through solar radiation elicit a small contribution to Earth's prograde annual nutation at a level of 100 μas (microarcseconds). Previously published estimates of this Sun-synchronous perturbation based on angular momentum series from global geophysical fluid models have however diverged, and within the present conventional nutation theory, the effect has been instead accounted for in an empirical manner based on analyzing residual spectra of observed celestial pole offsets. This study constitutes a first, tentative reassessment of the S1 signal in nutation by resorting to modern-day atmospheric reanalyses as well as available hydrodynamic solutions for diurnal oceanic angular momentum changes that are driven by daily air pressure variations at the water surface. We elucidate the global character of the S1 tide with particular regard to Earth rotation variations and investigate to which extent atmospheric and oceanic excitation terms from various sources can be superimposed. The combined influence of the principal diurnal tide on Earth's nutation, associated with both atmosphere and ocean dynamics, is found to yield a sound agreement with its observational evidence from geodetic VLBI (Very Long Baseline Interferometry) measurements.

  12. Angular momentum budget of the radiational S1 ocean tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Dobslaw, Henryk; Poropat, Lea; Salstein, David; Böhm, Johannes

    2016-04-01

    The balance of diurnal S1 oceanic angular momentum (OAM) variations through torques at the sea surface and the bottom topography is validated using both a barotropic and a baroclinic numerical tide model. This analysis discloses the extent to which atmosphere-driven S1 forward simulations are reliable for use in studies of high-frequency polar motion and changes in length-of-day. Viscous and dissipative torques associated with wind stress, bottom friction, as well as internal tidal energy conversion are shown to be small, and they are overshadowed by gravitational and pressure-related interaction forces. In particular, the zonal OAM variability of S1 is almost completely balanced by the water pressure torque on the local bathymetry, whereas in the prograde equatorial case also the air pressure torque on the seafloor as well as ellipsoidal contributions from the non-spherical atmosphere and solid Earth must be taken into account. Overall, the OAM budget is well closed in both the axial and the equatorial directions, thus allowing for an identification of the main diurnal angular momentum sinks in the ocean. The physical interaction forces are found to be largest at shelf breaks and continental slopes in low latitudes, with the most dominant contribution coming from the Indonesian archipelago.

  13. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G. P.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Brucato, J. R.; Bolli, P.; Massi, F.; Tofani, G.

    2015-12-01

    Comets are uniquely pristine bodies providing unique insights about the formation of our Solar System. In this work, we focus on a dynamically new comet as it enters the inner Solar System for the first time after residing for billion of years in the Oort Cloud. Such comets are particularly important because they are thought to be not differentiated by solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH3(1,1) emission at 23.7 GHz towards comet C/2012 S1 (ISON) using a new dual-feed K band receiver mounted on the Medicina 32-m antenna. We observed the comet close to its perihelion, from 25 to 29 November 2013, when its heliocentric distance changed from 0.25 AU to 0.03 AU. We derive an upper limit of Q(NH3) of about 2.5×1029 mol s-1 on 26 November, that is consistent with the last peak of water production rate of ∼2×1030 mol s-1 within the last few days before the perihelion.

  14. Osmo-, Thermo- and Ethanol- Tolerances of Saccharomyces cerevisiae S1

    PubMed Central

    Balakumar, Sandrasegarampillai; Arasaratnam, Vasanthy

    2012-01-01

    Saccharomyces cerevisiae S1, which is a locally isolated and improved strain showed viability at 40, 45 and 50°C and produced ethanol at 40, 43 and 45°C. When the cells were given heat shock at 45°C for 30min and grown at 40°C, 100% viability was observed for 60h, and addition of 200gL−1 ethanol has led to complete cell death at 30h. Heat shock given at 45°C (for 30min) has improved the tolerance to temperature induced ethanol shock leading to 37% viability at 30h. When the cells were subjected to ethanol (200gL−1 for 30 min) and osmotic shock (sorbitol 300gL−1), trehalose contents in the cells were increased. The heat shocked cells showed better viability in presence of added ethanol. Soy flour supplementation has improved the viability of S. cerevisiae S1 to 80% in presence of 100gL−1 added ethanol and to 60% in presence of 300gL−1sorbitol. In presence of sorbitol (200gL−1) and ethanol (50gL−1) at 40°C, 46% viability was retained by S. cerevisiae S1 at 48h and it was improved to 80% by soy flour supplementation. PMID:24031814

  15. Interaction of integrin β4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement.

    PubMed

    Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo; Zhou, Tingting; Xie, Lishi; Garcia, Joe G N; Jacobson, Jeffrey R

    2014-06-01

    We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute lung inury (ALI). While the mechanisms underlying these effects are not fully understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin β4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC signaling and their associations with ITGB4. Our studies confirmed ITGB4 and S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 µM, 5 min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3 association induced by S1P/HGF although a direct association was not detectable between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF-induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3 associations. Moreover, PLA confirmed a direct association between S1PR1 and S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced barrier enhancement. These results confirm an important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier regulation that may ultimately lead to new therapeutic targets for disorders characterized by increased vascular permeability including ALI.

  16. Lama glama αS1-casein: Identification of new polymorphisms in the CSN1S1 gene.

    PubMed

    Pauciullo, A; Gauly, M; Cosenza, G; Wagner, H; Erhardt, G

    2017-02-01

    South American camelids have been poorly genetically investigated and little information is available in llamas (Lama glama) regarding the diversity of the caseins at the protein and gene level. Exon skipping and duplication events previously reported in the αS1-casein gene (CSN1S1) led us to investigate the genetic variability at this locus. Seventy-two positive clones for the αS1-casein transcripts were analyzed and randomly sequenced. The comparative analysis of the sequences revealed 2 transitions, c.366A>G and c.690T>C, at the 10th nucleotide of exon 12 and 94 bp of exon 19, respectively. These SNP are responsible for 2 amino acid changes, Ile→Val in position 86 and Tyr→His in position 194 of the mature protein. Both polymorphisms clarify the genetic events behind the protein variants A and B. This result was confirmed by isoelectric focusing analysis of llama milk samples. Quick methods based on PCR-RFLP and allele-specific PCR were set up for allelic discrimination in a population of 128 animals. Based on genotyping results, 4 haplotypes were observed and the estimated frequencies indicated B as the most common haplotype (0.629) in the investigated population. These data add knowledge to the genetic variability of a species little investigated, and open opportunity for new investigation in the field of milk protein for South American camelids, including the possibility, in the future, to select alleles with favorable characteristics.

  17. Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor.

    PubMed

    Vachal, Petr; Toth, Leslie M; Hale, Jeffrey J; Yan, Lin; Mills, Sander G; Chrebet, Gary L; Koehane, Carol A; Hajdu, Richard; Milligan, James A; Rosenbach, Mark J; Mandala, Suzanne

    2006-07-15

    Novel series of sphingosine-1-phosphate (S1P) receptor agonists were developed through a systematic SAR aimed to achieve high selectivity for a single member of the S1P family of receptors, S1P1. The optimized structure represents a highly S1P1-selective and efficacious agonist: S1P1/S1P2, S1P1/S1P3, S1P1/S1P4>10,000-fold, S1P1/S1P5>600-fold, while EC50 (S1P1) <0.2 nM. In vivo experiments are consistent with S1P1 receptor agonism alone being sufficient for achieving desired lymphocyte-lowering effect.

  18. Complete genome sequence of Rhodospirillum rubrum type strain (S1).

    PubMed

    Munk, A Christine; Copeland, Alex; Lucas, Susan; Lapidus, Alla; Del Rio, Tijana Glavina; Barry, Kerrie; Detter, John C; Hammon, Nancy; Israni, Sanjay; Pitluck, Sam; Brettin, Thomas; Bruce, David; Han, Cliff; Tapia, Roxanne; Gilna, Paul; Schmutz, Jeremy; Larimer, Frank; Land, Miriam; Kyrpides, Nikos C; Mavromatis, Konstantinos; Richardson, Paul; Rohde, Manfred; Göker, Markus; Klenk, Hans-Peter; Zhang, Yaoping; Roberts, Gary P; Reslewic, Susan; Schwartz, David C

    2011-07-01

    Rhodospirillum rubrum (Esmarch 1887) Molisch 1907 is the type species of the genus Rhodospirillum, which is the type genus of the family Rhodospirillaceae in the class Alphaproteobacteria. The species is of special interest because it is an anoxygenic phototroph that produces extracellular elemental sulfur (instead of oxygen) while harvesting light. It contains one of the most simple photosynthetic systems currently known, lacking light harvesting complex 2. Strain S1(T) can grow on carbon monoxide as sole energy source. With currently over 1,750 PubMed entries, R. rubrum is one of the most intensively studied microbial species, in particular for physiological and genetic studies. Next to R. centenum strain SW, the genome sequence of strain S1(T) is only the second genome of a member of the genus Rhodospirillum to be published, but the first type strain genome from the genus. The 4,352,825 bp long chromosome and 53,732 bp plasmid with a total of 3,850 protein-coding and 83 RNA genes were sequenced as part of the DOE Joint Genome Institute Program DOEM 2002.

  19. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    SciTech Connect

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  20. Effect of anisotropy in the S=1 underscreened Kondo lattice

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Lacroix, Claudine; Iglesias, José Roberto; Coqblin, Bernard

    2014-12-01

    We study the effect of crystal field anisotropy in the underscreened S=1 Kondo lattice model. Starting from the two orbital Anderson lattice model and including a local anisotropy term, we show, through Schrieffer-Wolff transformation, that local anisotropy is equivalent to an anisotropic Kondo interaction (J∥≠J⊥). The competition and coexistence between ferromagnetism and Kondo effect in this effective model is studied within a generalized mean-field approximation. Several regimes are obtained, depending on the parameters, exhibiting or not coexistence of magnetic order and Kondo effect. Particularly, we show that a re-entrant Kondo phase at low temperature can be obtained. We are also able to describe phases where the Kondo temperature is smaller than the Curie temperature (TK

  1. Confinement and power balance in the S-1 spheromak

    SciTech Connect

    Levinton, F.M.; Meyerhofer, D.D.; Mayo, R.M.; Janos, A.C.; Ono, Y.; Ueda, Y.; Yamada, M.

    1989-07-01

    The confinement and scaling features of the S-1 spheromak have been investigated using magnetic, spectroscopic, and Thomson scattering data in conjunction with numerical modeling. Results from the multipoint Thomson scattering diagnostic shows that the central beta remains constant (/beta//sub to/ /approximately/ 5%) as the plasma current density increases from 0.68--2.1 MA/m/sup 2/. The density is observed to increase slowly over this range, while the central electron temperature increases much more rapidly. Analysis of the global plasma parameters shows a decrease in the volume average beta and energy confinement as the total current is increased. The power balance has been modeled numerically with a 0-D non-equilibrium time-dependent coronal model and is consistent with the experimental observations. 20 refs., 12 figs., 2 tabs.

  2. Transitive Lie groups on S^1\\times S^{2m}

    NASA Astrophysics Data System (ADS)

    Gorbatsevich, Vladimir V.

    2007-10-01

    The structure of Lie groups acting transitively on the direct product of a circle and an even-dimensional sphere is described. For products of two spheres of dimension >1 a similar problem has already been solved by other authors. The minimal transitive Lie groups on S^1 and S^{2m} are also indicated. As an application of these results, the structure of the automorphism group of one class of geometric structures, generalized quadrangles (a special case of Tits buildings) is considered. A conjecture put forward by Kramer is proved: the automorphism group of a connected generalized quadrangle of type (1,2m) always contains a transitive subgroup that is the direct product of a compact simple Lie group and a one-dimensional Lie group. Bibliography: 16 titles.

  3. Magnetoelectric Behavior from S =1 /2 Asymmetric Square Cupolas

    NASA Astrophysics Data System (ADS)

    Kato, Yasuyuki; Kimura, Kenta; Miyake, Atsushi; Tokunaga, Masashi; Matsuo, Akira; Kindo, Koichi; Akaki, Mitsuru; Hagiwara, Masayuki; Sera, Masakazu; Kimura, Tsuyoshi; Motome, Yukitoshi

    2017-03-01

    Magnetoelectric properties are studied by a combined experimental and theoretical study of a quasi-two-dimensional material composed of square cupolas, Ba(TiO )Cu4(PO4 ) 4 . The magnetization is measured up to the field above the saturation, and several anomalies are observed depending on the field directions. We propose a S =1 /2 spin model with Dzyaloshinskii-Moriya interactions, which reproduces the full magnetization curves well. Elaborating the phase diagram of the model, we show that the anomalies are explained by magnetoelectric phase transitions. Our theory also accounts for the scaling of the dielectric anomaly observed in the experiments. The results elucidate the crucial role of the in-plane component of Dzyaloshinskii-Moriya interactions, which is induced by the noncoplanar buckling of a square cupola. We also predict a "hidden" phase and another magnetoelectric response, both of which appear in a nonzero magnetic field.

  4. Comparisons of absolute gravimeters (COOMET.M.G-S1)

    NASA Astrophysics Data System (ADS)

    Vinnichenko, Mr Alexander; Germak, Alessandro, Dr

    2017-01-01

    This report describes the results of the RMO supplementary comparison COOMET.M.G-S1 (also known as bilateral comparison COOMET 634/UA/14). The comparison measurements between the two participants NSC 'IM' (pilot laboratory) and INRIM were started in December 2015 and finished in January 2016. Participants of comparisons were conducted at their national standards the measurements of the free fall acceleration in gravimetric point laboratory of absolute gravimetry of INRIM named INRiM.2. Absolute measurements of gravimetric acceleration were conducted by ballistic gravimeters. The agreement between the two participants is good. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  5. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    PubMed

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases.

  6. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection.

    PubMed

    Yung, Bryan S; Brand, Cameron S; Xiang, Sunny Y; Gray, Charles B B; Means, Christopher K; Rosen, Hugh; Chun, Jerold; Purcell, Nicole H; Brown, Joan Heller; Miyamoto, Shigeki

    2017-02-01

    Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P1, S1P2, and S1P3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to Gq. We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα13 but not Gα12, Gαq, or Gαi. Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P3 KO mouse heart. CYM-51736, an S1P3-specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P3 receptor- and Gα13-mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P3 receptors could provide therapeutic benefits in ischemic heart disease.

  7. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    PubMed

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  8. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors

    PubMed Central

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E.; O’Carroll, Simon J.; Graham, E. Scott

    2016-01-01

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors. PMID:26813587

  9. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    PubMed

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  10. Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

    PubMed Central

    Mochiki, E; Ogata, K; Ohno, T; Toyomasu, Y; Haga, N; Fukai, Y; Aihara, R; Ando, H; Uchida, N; Asao, T; Kuwano, H

    2012-01-01

    Background: A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. Methods: Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m−2 twice daily) on days 1–14 plus paclitaxel (60 mg m−2) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m−2 twice daily) on days 1–21 plus cisplatin (60 mg m−2) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin. Conclusion: S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials. PMID:22617130

  11. Sphingosine 1-phosphate receptor 1 (S1P(1)) upregulation and amelioration of experimental autoimmune encephalomyelitis by an S1P(1) antagonist.

    PubMed

    Cahalan, Stuart M; Gonzalez-Cabrera, Pedro J; Nguyen, Nhan; Guerrero, Miguel; Cisar, Elizabeth A George; Leaf, Nora B; Brown, Steven J; Roberts, Edward; Rosen, Hugh

    2013-02-01

    Sphingosine 1-phosphate receptor 1 (S1P(1)) is a G protein-coupled receptor that is critical for proper lymphocyte development and recirculation. Agonists to S1P(1) are currently in use clinically for the treatment of multiple sclerosis, and these drugs may act on both S1P(1) expressed on lymphocytes and S1P(1) expressed within the central nervous system. Agonists to S1P(1) and deficiency in S1P(1) both cause lymphocyte sequestration in the lymph nodes. In the present study, we show that S1P(1) antagonism induces lymphocyte sequestration in the lymph nodes similar to that observed with S1P(1) agonists while upregulating S1P(1) on lymphocytes and endothelial cells. Additionally, we show that S1P(1) antagonism reverses experimental autoimmune encephalomyelitis in mice without acting on S1P(1) expressed within the central nervous system, demonstrating that lymphocyte sequestration via S1P(1) antagonism is sufficient to alleviate autoimmune pathology.

  12. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

    PubMed

    Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

    2016-08-01

    Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice.

  13. Possible Dust Models for C/2012 S1

    NASA Astrophysics Data System (ADS)

    Yanamandra-Fisher, P. A.

    2014-12-01

    Comet C/2012 S1 (ISON) provided a great opportunity to study a dynamically new Oort-cloud comet on its initial and only passage through the inner solar system. Contrary to expectations, the comet's activity fluctuated from high through a quiescent phase, and a major outburst days before its perihelion passage, ending in a dramatic race to complete disintegration on perihelion day, 28 November 2013. Amateur observations to professional ground-based, sub-orbital telescopes indicate the various changes of visible factors such as Afrho, a proxy for dust activity, and the measured production rates for water, consistent with the disintegration of the nucleus. Hines et al. (2013; ApJ Lett. 780) detected positive polarization in the inner coma and negative polarization in the outer coma, indicative of a jet, independently confirmed by Li et al. (2013, ApJ Lett., 779). Thermal emission observations of the comet pre-perihelion from NAOJ/Subaru/COMICS, a mid-infrared spectrometer, indicated a body with an equivalent brightness temperature of 265K (Ootsubo et al., 2013, ACM, Helsinki,FI); thermal observations acquired at the NASA/Infrared Telescope Facility (IRTF) with The Aerospace Corporation spectrometer (BASS, PI. R. Russell), before and after the November 12, 2013 outburst observed by the CIOC_ISON amateur network, indicates a brightness temperature of 330K and the presence, albeit weak, of the 11.3-micron crystalline silicate feature (Sitko et al., 2014, LPI abstract 1537). A Monte Carlo comet dust tail model, applied to extract the dust environment parameters of comet C/2012 S1 (ISON) from both Earth-based and Solar and Heliospheric Observatory (SOHO) calibrated observations, performed from about 6 AU (inbound), to right after perihelion passage, when just a small portion of the original comet nucleus survived in the form of a cloud of tiny particles, indicates that particles underwent disintegration and fragmentation (Moreno et al., 2014, ApJ Lett., 791). Ongoing work

  14. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    PubMed

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  15. Outgassing and chemical evolution of C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Dello Russo, Neil; Vervack, Ronald J.; Kawakita, Hideyo; Cochran, Anita; McKay, Adam J.; Harris, Walter M.; Weaver, Harold A.; Lisse, Carey M.; DiSanti, Michael A.; Kobayashi, Hitomi; Biver, Nicolas; Bockelée-Morvan, Dominique; Crovisier, Jacques; Opitom, Cyrielle; Jehin, Emmanuel

    2015-11-01

    Volatile production rates, relative abundances, rotational temperatures, and spatial distributions in the coma were measured in C/2012 S1 (ISON) using long-slit high-dispersion (λ/Δλ ~ 25,000) infrared spectroscopy as part of a worldwide observing campaign. Spectra were obtained on UT 2013 October 26 and 28 with NIRSPEC at the W. M. Keck Observatory, and UT 2013 November 19 and 20 with CSHELL at the NASA IRTF. H2O was detected on all dates, with production rates increasing by about a factor of 40 between October 26 (Rh = 1.12 AU) and November 20 (Rh = 0.43 AU). Short-term variability of H2O was also seen as the production rate increased by nearly a factor of two during observations obtained over a period of about six hours on November 19. C2H6, CH3OH and CH4 abundances were slightly depleted relative to H2O in ISON compared to mean values for comets measured at infrared wavelengths. On the November dates, C2H2, HCN and OCS abundances relative to H2O appear to be close to the range of mean values, whereas H2CO and NH3 were significantly enhanced. We will compare derived chemical abundances in ISON to other comets measured with infrared spectroscopy.

  16. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

    PubMed

    Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

    2015-06-01

    Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

  17. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

    PubMed

    Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

    2017-01-01

    Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. .

  18. ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs.

    PubMed

    Ren, Kun; Lu, Yan-Ju; Mo, Zhong-Cheng; -Liu, Xing; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Li, Li; Zhang, Qing-Hai; Yi, Guang-Hui

    2017-02-08

    Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

  19. Sphingosine 1-phosphate (S1P) receptor agonists mediate pro-fibrotic responses in normal human lung fibroblasts via S1P2 and S1P3 receptors and Smad-independent signaling.

    PubMed

    Sobel, Katrin; Menyhart, Katalin; Killer, Nina; Renault, Bérengère; Bauer, Yasmina; Studer, Rolf; Steiner, Beat; Bolli, Martin H; Nayler, Oliver; Gatfield, John

    2013-05-24

    Synthetic sphingosine 1-phosphate receptor 1 modulators constitute a new class of drugs for the treatment of autoimmune diseases. Sphingosine 1-phosphate (S1P) signaling, however, is also involved in the development of fibrosis. Using normal human lung fibroblasts, we investigated the induction of fibrotic responses by the S1P receptor (S1PR) agonists S1P, FTY720-P, ponesimod, and SEW2871 and compared them with the responses induced by the known fibrotic mediator TGF-β1. In contrast to TGF-β1, S1PR agonists did not induce expression of the myofibroblast marker α-smooth muscle actin. However, TGF-β1, S1P, and FTY720-P caused robust stimulation of extracellular matrix (ECM) synthesis and increased pro-fibrotic marker gene expression including connective tissue growth factor. Ponesimod showed limited and SEW2871 showed no pro-fibrotic potential in these readouts. Analysis of pro-fibrotic signaling pathways showed that in contrast to TGF-β1, S1PR agonists did not activate Smad2/3 signaling but rather activated PI3K/Akt and ERK1/2 signaling to induce ECM synthesis. The strong induction of ECM synthesis by the nonselective agonists S1P and FTY720-P was due to the stimulation of S1P2 and S1P3 receptors, whereas the weaker induction of ECM synthesis at high concentrations of ponesimod was due to a low potency activation of S1P3 receptors. Finally, in normal human lung fibroblast-derived myofibroblasts that were generated by TGF-β1 pretreatment, S1P and FTY720-P were effective stimulators of ECM synthesis, whereas ponesimod was inactive, because of the down-regulation of S1P3R expression in myofibroblasts. These data demonstrate that S1PR agonists are pro-fibrotic via S1P2R and S1P3R stimulation using Smad-independent pathways.

  20. The turbomachine blading design using S2-S1 approach

    NASA Technical Reports Server (NTRS)

    Luu, T. S.; Bencherif, L.; Viney, B.; Duc, J. M. Nguyen

    1991-01-01

    The boundary conditions corresponding to the design problem when the blades being simulated by the bound vorticity distribution are presented. The 3D flow is analyzed by the two steps S2 - S1 approach. In the first step, the number of blades is supposed to be infinite, the vortex distribution is transformed into an axisymmetric one, so that the flow field can be analyzed in a meridional plane. The thickness distribution of the blade producing the flow channel striction is taken into account by the modification of metric tensor in the continuity equation. Using the meridional stream function to define the flow field, the mass conservation is satisfied automatically. The governing equation is deduced from the relation between the azimuthal component of the vorticity and the meridional velocity. The value of the azimuthal component of the vorticity is provided by the hub to shroud equilibrium condition. This step leads to the determination of the axisymmetric stream sheets as well as the approximate camber surface of the blade. In the second step, the finite number of blades is taken into account, the inverse problem corresponding to the blade to blade flow confined in each stream sheet is analyzed. The momentum equation implies that the free vortex of the absolute velocity must be tangential to the stream sheet. The governing equation for the blade to blade flow stream function is deduced from this condition. At the beginning, the upper and the lower surfaces of the blades are created from the camber surface obtained from the first step with the assigned thickness distribution. The bound vorticity distribution and the penetrating flux conservation applied on the presumed blade surface constitute the boundary conditions of the inverse problem. The detection of this flux leads to the rectification of the geometry of the blades.

  1. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Bolli, P.; Brucato, J.; Massi, F.; Tofani, G.

    2014-07-01

    Comets are pristine bodies of the Solar System and their studies can give precious hints on the formation of the Solar System itself. New comets, coming form the Oort Colud at their first passage close to the Sun, are particularly important, because they are not differentiated by the Solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH_3(1,1) emission at 23.7 GHz in comet C/2012 S1 ISON using a new dual-feed K-band receiver mounted on the Medicina 32-m antenna. We observed the comet once close to its perihelion, from 2013 Nov. 25 to Nov. 28, when its heliocentric distance changed from 0.25 au to 0.03 au. We integrated about 6 hrs per day, obtaining high-spectral-resolution (1 km/s) spectra with a typical rms noise of 10 mK. Such sensitivity allowed us to derive an upper limit of Q(NH_3) of about 2.5 ×10^{29} mol/s on November 26. This upper limit would correspond to a Q(H_2O) of about 2.5 ×10^{31} mol/s, assuming the typical Q(H_2O)/Q(NH_3) ratio of 100. These findings confirm that no significant Q(H_2O) enhancement happened near the perihelion, consistent with a definitive decrease of molecules production rate.

  2. WILL COMET ISON (C/2012 S1) SURVIVE PERIHELION?

    SciTech Connect

    Knight, Matthew M.; Walsh, Kevin J.

    2013-10-10

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ∼200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm{sup –3} are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm{sup –3}, with the chances of disruption increasing for lower density, faster prograde rotation, and increasing elongation of the nucleus. Given current constraints on ISON's nucleus properties and the typically determined values for these properties among all comets, we find tidal disruption to be unlikely unless other factors (e.g., spin-up via torquing) affect ISON substantially. Whether or not disruption occurs, the largest remnant must be big enough to survive subsequent mass loss due to sublimation in order for ISON to remain a viable comet well after perihelion.

  3. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    PubMed

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells.

  4. Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

    PubMed

    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

    Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

  5. Novel selective allosteric and bitopic ligands for the S1P(3) receptor.

    PubMed

    Jo, Euijung; Bhhatarai, Barun; Repetto, Emanuela; Guerrero, Miguel; Riley, Sean; Brown, Steven J; Kohno, Yasushi; Roberts, Edward; Schürer, Stephan C; Rosen, Hugh

    2012-12-21

    Sphingosine 1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions, including lymphocyte trafficking and vascular development, by activating G protein-coupled receptors for S1P, namely, S1P(1) through S1P(5). Here, we map the S1P(3) binding pocket with a novel allosteric agonist (CYM-5541), an orthosteric agonist (S1P), and a novel bitopic antagonist (SPM-242). With a combination of site-directed mutagenesis, ligand competition assay, and molecular modeling, we concluded that S1P and CYM-5541 occupy different chemical spaces in the ligand binding pocket of S1P(3). CYM-5541 allowed us to identify an allosteric site where Phe263 is a key gate-keeper residue for its affinity and efficacy. This ligand lacks a polar moiety, and the novel allosteric hydrophobic pocket permits S1P(3) selectivity of CYM-5541 within the highly similar S1P receptor family. However, a novel S1P(3)-selective antagonist, SPM-242, in the S1P(3) pocket occupies the ligand binding spaces of both S1P and CYM-5541, showing its bitopic mode of binding. Therefore, our coordinated approach with biochemical data and molecular modeling, based on our recently published S1P(1) crystal structure data in a highly conserved set of related receptors with a shared ligand, provides a strong basis for the successful optimization of orthosteric, allosteric, and bitopic modulators of S1P(3).

  6. Study on the anatomy of the lumbosacral anterior great vessels pertinent to L5/S1 anterior interbody surgery with computer tomography angiography.

    PubMed

    Liu, Liehua; Liang, Yong; Zhou, Qiang; Zhang, Hong; Wang, Haoming; Li, Songtao; Zhao, Chen; Hou, Tianyong; Liu, Ling

    2014-12-01

    We investigate the anatomy of the lumbosacral anterior great vessels using computer tomography (CT) angiography before L5/S1 anterior interbody surgery. Sixty-two adult patients were selected. The location of the abdominal aortic bifurcation and common iliac venous confluence in the lumbar vertebrae and the anatomic parameters of the iliac vascular space (e.g., distances from the included angle vertex of the iliac vascular space to the median sagittal plane and to the inferior boundary of L5 and distances between the left and right iliac vessels on the inferior boundary of L5 and on the superior boundary of S1) were analysed. Overall, 67.73% of the 62 cases had an abdominal aortic bifurcation located at L4 and L4/5 intervertebral disc; 61.29%, the common iliac venous confluence located at L5. The four distances mentioned above were 0.98 cm ± 0.38 cm, 2.01 cm ± 1.26 cm, 3.11 cm ± 1.35 cm and 4.34 cm ± 1.10 cm, respectively. A classification system of types A, B and C was developed. The calculated L5/S1 intervertebral space exposure percentages of types A, B and C were 32.21%, 82.58% and 54.68%, respectively. During L5/S1 anterior interbody surgery, type B intervertebral discs can be exposed conveniently, preventing injury of the iliac vessels, which was also observed in 54.68% and 32.21% of the type C and type A discs, respectively. Because the type A intervertebral disc has minimal exposure, the risk of iliac vascular injury is relatively high in these patients.

  7. Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.

    PubMed

    Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

    2015-10-01

    Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis.

  8. The SphKs/S1P/S1PR1 axis in immunity and cancer: more ore to be mined.

    PubMed

    Jin, Lei; Liu, Wei-Ren; Tian, Meng-Xin; Fan, Jia; Shi, Ying-Hong

    2016-04-29

    Over the past two decades, huge amounts of research were launched to understand the functions of sphingosine. Many pathways were uncovered that convey the relative functions of biomacromolecules. In this review, we discuss the recent advances of the role of the SphKs/S1P/S1PR1 axis in immunity and cancer. Finally, we investigate the therapeutic potential of new drugs that target S1P signaling in cancer therapy.

  9. Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.

    PubMed

    Lee, Hui Min; Lo, Kwok-Wai; Wei, Wenbin; Tsao, Sai Wah; Chung, Grace Tin Yun; Ibrahim, Maha Hafez; Dawson, Christopher W; Murray, Paul G; Paterson, Ian C; Yap, Lee Fah

    2017-02-27

    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1 and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is over-expressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease.

  10. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

    PubMed

    Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

    2016-05-10

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.

  11. Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like head-group interactions

    PubMed Central

    Gonzalez-Cabrera, Pedro J.; Jo, Euijung; Sanna, M. Germana; Brown, Steven; Leaf, Nora; Marsolais, David; Schaeffer, Marie-Therese; Chapman, Jacqueline; Cameron, Michael; Guerrero, Miguel; Roberts, Edward; Rosen, Hugh

    2008-01-01

    Strong evidence exists for interactions of zwitterionic phosphate and amine groups in Sphingosine-1 phosphate (S1P) to conserved R and E residues present at the extracellular face of transmembrane-3 (TM3) of S1P receptors. The contribution of R120 and E121 for high affinity ligand-receptor interactions is essential, as single-point R120A or E121A S1P1 mutants neither bind S1P nor transduce S1P function. Because S1P receptors are therapeutically interesting, identifying potent selective agonists with different binding modes and in vivo efficacy is of pharmacological importance. Here we describe a modestly water-soluble highly-selective S1P1 agonist (CYM-5442) that does not require R120 or E121 residues for activating S1P1-dependent p42/p44 MAPK phosphorylation, which defines a new hydrophobic pocket in S1P1. CYM-5442 is a full agonist in vitro for S1P1 internalization, phosphorylation and ubiquitination. Importantly, CYM-5442 was a full agonist for induction and maintenance of S1P1-dependent lymphopenia, decreasing B-lymphocytes by 65% and T-lymphocytes by 85% of vehicle. Induction of CYM-5442 lymphopenia was dose and time-dependent, requiring serum concentrations in the 50 nM range. In vitro measures of S1P1 activation by CYM-5442 were non-competitively inhibited by a specific S1P1 antagonist (W146), competitive for S1P, FTY720-P and SEW2871. In addition, lymphopenia by CYM-5442 was reversed by W146 administration or upon pharmacokinetic agonist clearance. Pharmacokinetics in mice also indicated that CYM-5442 partitions significantly in central nervous tissue. These data show that CYM-5442 activates S1P1-dependent pathways in vitro and to levels of full efficacy in vivo through a hydrophobic pocket, separable from the orthosteric site of S1P binding that is headgroup dependent. PMID:18708635

  12. Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise

    PubMed Central

    Silva, Vagner Ramon Rodrigues; Katashima, Carlos Kiyoshi; Bueno Silva, Carla G.; Lenhare, Luciene; Micheletti, Thayana Oliveira; Camargo, Rafael Ludemann; Ghezzi, Ana Carolina; Camargo, Juliana Alves; Assis, Alexandre Moura; Tobar, Natalia; Morari, Joseane; Razolli, Daniela S.; Moura, Leandro Pereira; Pauli, José Rodrigo; Cintra, Dennys Esper; Velloso, Lício Augusto; Saad, Mario J.A; Ropelle, Eduardo Rochete

    2017-01-01

    Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process. PMID:28039439

  13. Ligand-binding pocket shape differences between S1P1 and S1P3 determine efficiency of chemical probe identification by uHTS

    PubMed Central

    Schürer, Stephan C.; Brown, Steven J.; Cabrera, Pedro Gonzales; Schaeffer, Marie-Therese; Chapman, Jacqueline; Jo, Euijung; Chase, Peter; Spicer, Tim; Hodder, Peter; Rosen, Hugh

    2008-01-01

    We have studied the Sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonists chemotypes for each of the S1P1 and S1P3 receptors. uHTS for S1P1 was more effective than for S1P3, with many selective, low nanomolar hits of proven mechanism emerging for. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for sub-type selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of head-group interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 vs. S1P3 in this closely related receptor family. PMID:18590333

  14. Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, trafficking, and signaling of S1P1.

    PubMed

    Wilkerson, Brent A; Grass, G Daniel; Wing, Shane B; Argraves, W Scott; Argraves, Kelley M

    2012-12-28

    Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function.

  15. A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders

    PubMed Central

    Huwiler, Andrea; Bourquin, Florence; Kotelevets, Nataliya; Pastukhov, Oleksandr; Capitani, Guido; Grütter, Markus G.; Zangemeister-Wittke, Uwe

    2011-01-01

    Sphingosine-1-phosphate (S1P) regulates a broad spectrum of fundamental cellular processes like proliferation, death, migration and cytokine production. Therefore, elevated levels of S1P may be causal to various pathologic conditions including cancer, fibrosis, inflammation, autoimmune diseases and aberrant angiogenesis. Here we report that S1P lyase from the prokaryote Symbiobacterium thermophilum (StSPL) degrades extracellular S1P in vitro and in blood. Moreover, we investigated its effect on cellular responses typical of fibrosis, cancer and aberrant angiogenesis using renal mesangial cells, endothelial cells, breast (MCF-7) and colon (HCT 116) carcinoma cells as disease models. In all cell types, wild-type StSPL, but not an inactive mutant, disrupted MAPK phosphorylation stimulated by exogenous S1P. Functionally, disruption of S1P receptor signaling by S1P depletion inhibited proliferation and expression of connective tissue growth factor in mesangial cells, proliferation, migration and VEGF expression in carcinoma cells, and proliferation and migration of endothelial cells. Upon intravenous injection of StSPL in mice, plasma S1P levels rapidly declined by 70% within 1 h and then recovered to normal 6 h after injection. Using the chicken chorioallantoic membrane model we further demonstrate that also under in vivo conditions StSPL, but not the inactive mutant, inhibited tumor cell-induced angiogenesis as an S1P-dependent process. Our data demonstrate that recombinant StSPL is active under extracellular conditions and holds promise as a new enzyme therapeutic for diseases associated with increased levels of S1P and S1P receptor signaling. PMID:21829623

  16. Genetic characterization of three qnrS1-harbouring multidrug-resistance plasmids and qnrS1-containing transposons circulating in Ho Chi Minh City, Vietnam

    PubMed Central

    Le, Vien; Nhu, Nguyen Thi Khanh; Cerdeno-Tarraga, Ana; Campbell, James I.; Tuyen, Ha Thanh; Nhu, Tran Do Hoang; Tam, Pham Thi Thanh; Schultsz, Constance; Thwaites, Guy; Thomson, Nicholas R.

    2015-01-01

    Plasmid-mediated quinolone resistance (PMQR) refers to a family of closely related genes that confer decreased susceptibility to fluoroquinolones. PMQR genes are generally associated with integrons and/or plasmids that carry additional antimicrobial resistance genes active against a range of antimicrobials. In Ho Chi Minh City (HCMC), Vietnam, we have previously shown a high frequency of PMQR genes within commensal Enterobacteriaceae. However, there are limited available sequence data detailing the genetic context in which the PMQR genes reside, and a lack of understanding of how these genes spread across the Enterobacteriaceae. Here, we aimed to determine the genetic background facilitating the spread and maintenance of qnrS1, the dominant PMQR gene circulating in HCMC. We sequenced three qnrS1-carrying plasmids in their entirety to understand the genetic context of these qnrS1-embedded plasmids and also the association of qnrS1-mediated quinolone resistance with other antimicrobial resistance phenotypes. Annotation of the three qnrS1-containing plasmids revealed a qnrS1-containing transposon with a closely related structure. We screened 112 qnrS1-positive commensal Enterobacteriaceae isolated in the community and in a hospital in HCMC to detect the common transposon structure. We found the same transposon structure to be present in 71.4 % (45/63) of qnrS1-positive hospital isolates and in 36.7 % (18/49) of qnrS1-positive isolates from the community. The resulting sequence analysis of the qnrS1 environment suggested that qnrS1 genes are widely distributed and are mobilized on elements with a common genetic background. Our data add additional insight into mechanisms that facilitate resistance to multiple antimicrobials in Gram-negative bacteria in Vietnam. PMID:26272054

  17. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

    PubMed

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

  18. Moesin Controls Clathrin-Mediated S1PR1 Internalization in T Cells

    PubMed Central

    Nomachi, Akira; Yoshinaga, Masanori; Liu, Jaron; Kanchanawong, Pakorn; Tohyama, Kiyoshi; Thumkeo, Dean; Watanabe, Takeshi; Narumiya, Shuh; Hirata, Takako

    2013-01-01

    The lipid mediator sphingosine 1-phosphate (S1P) regulates a wide range of cellular activities, including vascular maturation, angiogenesis, and immune-cell trafficking. Among the five known receptors for S1P (S1PR1-S1PR5), S1PR1 is a critical regulator of lymphocyte trafficking: its signaling is required for lymphocyte egress from lymphoid organs, while its down-modulation by agonist-induced internalization is a prerequisite for lymphocyte entry into lymphoid organs from the bloodstream. Despite the importance of S1PR1 down-regulation in determining lymphocyte behavior, the molecular mechanism of its internalization in lymphocytes has not been defined. Here we show that agonist-induced S1PR1 internalization in T cells occurs via clathrin-mediated endocytosis and is regulated by moesin, an ezrin-radixin-moesin (ERM) family member. In S1P-stimulated T cells, S1PR1 relocalized within clathrin-coated vesicles (CCVs) and early endosomes, and S1PR1 internalization was blocked when clathrin was pharmacologically inhibited. Stimulating moesin-deficient T cells with S1P failed to induce S1PR1 internalization and CCV formation. Furthermore, treating moesin-deficient mice with FTY720, an S1P receptor agonist known to internalize S1PR1, caused delayed lymphopenia, and lymphocytes isolated from FTY720-treated moesin-deficient mice still responded to S1P ex vivo in chemotaxis assays. These results reveal a novel role for moesin in regulating clathrin-dependent S1PR1 internalization through CCV formation. PMID:24358210

  19. 26 CFR 31.3121(s)-1 - Concurrent employment by related corporations with common paymaster.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with common paymaster. 31.3121(s)-1 Section 31.3121(s)-1 Internal Revenue INTERNAL REVENUE SERVICE... Revenue Code of 1954) General Provisions § 31.3121(s)-1 Concurrent employment by related corporations with... this section. Section 3121(s) and this section apply only to remuneration disbursed in the form...

  20. Therapeutic efficacy and safety of S-1-based combination therapy compare with S-1 monotherapy following gemcitabine failure in pancreatic cancer: a meta-analysis

    PubMed Central

    Lu, Sinan; Zhang, Yuan; Zhou, Xiaohu; Zhou, Dongkai; Yang, Qifan; Ju, Bingjie; Zhao, Xinyi; Hu, Zhenhua; Xie, Haiyang; Zhou, Lin; Zheng, Shusen; Wang, Weilin

    2016-01-01

    S-1 monotherapy is widely used following gemcitabine failure in pancreatic cancer, especially in East Asia. We performed a meta-analysis to determine whether S-1-based combination therapy had better efficacy and safety compared with S-1 monotherapy. We searched Pubmed, Web of Science, ClinicalTrials.gov, and Cochrane CENTRAL and subsequently included five trials with a total of 690 patients. The combined hazard ratio (HR) or risk ratio; the corresponding 95% confidence intervals of progression-free survival, overall survival, and overall response rate; and grade 3–4 adverse events were examined. Five randomized controlled trials were included. Meta-analysis demonstrated S-1-based combination therapy significantly increased progression-free survival (HR = 0.78, 95% confidence interval [CI]: 0.67–0.90, p = 0.0009) and overall response rate (HR = 1.74, 95% CI: 1.20–2.52, p = 0.003). Evidence was insufficient to confirm that S-1-based combined regimens improved overall survival (HR = 0.87, 95% CI: 0.75–1.00, p = 0.05). There was no significant difference in adverse events between the two treatment arms. In conclusion, S-1-based combination therapy improved progression-free survival and overall response rate compared to S-1 monotherapy with acceptable toxicity. PMID:27833144

  1. Therapeutic efficacy and safety of S-1-based combination therapy compare with S-1 monotherapy following gemcitabine failure in pancreatic cancer: a meta-analysis.

    PubMed

    Lu, Sinan; Zhang, Yuan; Zhou, Xiaohu; Zhou, Dongkai; Yang, Qifan; Ju, Bingjie; Zhao, Xinyi; Hu, Zhenhua; Xie, Haiyang; Zhou, Lin; Zheng, Shusen; Wang, Weilin

    2016-11-11

    S-1 monotherapy is widely used following gemcitabine failure in pancreatic cancer, especially in East Asia. We performed a meta-analysis to determine whether S-1-based combination therapy had better efficacy and safety compared with S-1 monotherapy. We searched Pubmed, Web of Science, ClinicalTrials.gov, and Cochrane CENTRAL and subsequently included five trials with a total of 690 patients. The combined hazard ratio (HR) or risk ratio; the corresponding 95% confidence intervals of progression-free survival, overall survival, and overall response rate; and grade 3-4 adverse events were examined. Five randomized controlled trials were included. Meta-analysis demonstrated S-1-based combination therapy significantly increased progression-free survival (HR = 0.78, 95% confidence interval [CI]: 0.67-0.90, p = 0.0009) and overall response rate (HR = 1.74, 95% CI: 1.20-2.52, p = 0.003). Evidence was insufficient to confirm that S-1-based combined regimens improved overall survival (HR = 0.87, 95% CI: 0.75-1.00, p = 0.05). There was no significant difference in adverse events between the two treatment arms. In conclusion, S-1-based combination therapy improved progression-free survival and overall response rate compared to S-1 monotherapy with acceptable toxicity.

  2. S1P3 confers differential S1P migration by autoreactive and non-autoreactive immature B cells and is required for normal B cell development

    PubMed Central

    Donovan, Erin E.; Pelanda, Roberta; Torres, Raul M.

    2010-01-01

    SUMMARY During B cell development, immature B cell fate is determined by whether the B cell antigen receptor is engaged in the bone marrow. Immature B cells that are non-autoreactive continue maturation and emigrate from the marrow whereas autoreactive immature B cells remain and are tolerized. However, the microenvironment where these events occur and the chemoattractants responsible for immature B cell trafficking within and out of the bone marrow remain largely undefined. Sphingosine 1-phosphate (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte egress and in this study we investigated whether S1P contributed to B cell development, egress and positioning within the bone marrow. Our findings show that immature B cells are chemotactic towards S1P but that this response is dependent on antigen receptor specificity: non-autoreactive, but not autoreactive, immature B cells migrate towards S1P and are shown to require S1P3 receptor for this response. Despite this response, S1P3 is shown not to facilitate immature B cell egress but is required for normal B cell development including the positioning of transitional B cells within bone marrow sinusoids. These data indicate that S1P3 signaling directs immature B cells to a bone marrow microenvironment important for both tolerance induction and maturation. PMID:20039302

  3. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts

    PubMed Central

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). The conservation of both C/S1 bZIP interactions and SIRT remains poorly characterized in non-model species, leaving their evolutionary origin uncertain and limiting crop research. In this work, we explored recently published plant sequencing data to establish a detailed phylogeny of C and S1 bZIPs, investigating their intertwined role in plant evolution, and the origin of SIRT. Our analyses clarified C and S1 bZIP orthology relationships in angiosperms, and identified S1 sequences in gymnosperms. We experimentally showed that the gymnosperm orthologs are regulated by SIRT, tracing back the origin of this unique regulatory mechanism to the ancestor of seed plants. Additionally, we discovered an earlier S ortholog in the charophyte algae Klebsormidium flaccidum, together with a C ortholog. This suggests that C and S groups originated by duplication from a single algal proto-C/S ancestor. Based on our observations, we propose a model wherein the C/S1 bZIP dimer network evolved in seed plants from pre-existing C/S bZIP interactions. PMID:27457880

  4. S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells

    PubMed Central

    Wang, Dongmei; Zhao, Zhenwen; Caperell-Grant, Andrea; Yang, Gong; Mok, Samuel C.; Liu, Jinsong; Bigsby, Robert M.; Xu, Yan

    2009-01-01

    Epithelial ovarian cancer (EOC) arises from the epithelial layer covering the surface of ovaries and intra-peritoneal metastasis is commonly observed at diagnosis. Sphingosine-1-phosphate (S1P), a bioactive lipid signaling molecule, is potentially involved in EOC tumorigenesis. We have found that S1P is elevated in human EOC ascites. We show that physiologically relevant concentrations of S1P stimulate migration and invasion of EOC cells, but inhibit migration of human ovarian surface epithelial (HOSE) cells. In addition, S1P inhibits lysophosphatidic acid (LPA)-induced cell migration in HOSE, but not in EOC cells. We have provided the first line of evidence that the expression levels of S1P receptor subtypes are not the only determinants for how cells respond to S1P. Even though S1P1 is expressed and functional in HOSE cells, the inhibitory effect mediated by S1P2 is dominant in those cells. The cellular pre-existing stress fibers are also important determinants for the migratory response to S1P. Differential S1P-induced morphology changes are noted in EOC and HOSE cells. Pre-existing stress fibers in HOSE cells are further enhanced by S1P treatment, resulting in the negative migratory response to S1P. By contrast, EOC cells lost stress fibers and S1P treatment induces filopodium-like structures at cell edges, which correlates with increased cell motility. In addition, inhibition of the protein kinase C pathway is likely to be involved in the inhibitory effect of S1P on LPA-induced cell migration in HOSE cells. These findings are important for the development of new therapeutics targeting S1P and LPA in EOC. PMID:18645009

  5. A survey of the physical health status of pupils aged 10-14 years in Standards 3-5 at three schools in New Crossroads, near Cape Town in the Western Cape.

    PubMed

    Ramphele, M A; Heap, M; Trollip, D K

    1995-10-01

    Although adolescence is most commonly associated with risk-taking behaviour, mortality due to poverty-related conditions is high among black African children aged 10-14 years. This paper describes a study carried out in October 1991 to assess the physical health status of 860 underprivileged pupils aged 10-14 years in Standards 3-5 at three schools in New Crossroads, near Cape Town. Data on nutritional status, age at menarche, blood pressure, eyesight, physical abnormalities, injuries and use of hospitals were obtained. The response rate was 90%. Of all the children, 7.2% were below the 5th percentile weight-for-age. The proportion of boys (13.1%) below the 5th percentile weight-for-age was significantly higher than that of girls (3.7%). Of all the children, 19.5% were below the 5th percentile height-for-age. The proportion of boys (24.4%) below the 5th percentile height-for-age was also significantly higher than that of girls (16.7%). The average age at menarche was 13 years, similar to that (12.8 years) reported for the UK. In 5% of the children, the diastolic blood pressure was > 90 mmHg and the findings show some increase with age. Red Cross War Memorial Children's Hospital accounted for 30.9% of hospital attendances. 'Chest' complaints (19.5%) were frequent reasons for consultations, while 15.2% of the children reported being injured, with car accidents (16.0%), fractures (27.5%) and burns (20.6%) being the most common injuries. It is suggested that the provision of a 24-hour day hospital will ease the load on the referral hospital, i.e. Red Cross War Memorial Children's Hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Phytosphingosine 1-phosphate: a high affinity ligand for the S1P(4)/Edg-6 receptor.

    PubMed

    Candelore, Mari Rios; Wright, Michael J; Tota, Laurie M; Milligan, James; Shei, Gan-ju; Bergstrom, James D; Mandala, Suzanne M

    2002-09-27

    It has been reported recently that the phosphorylated form of the immunomodulator FTY720 activates sphingosine 1-phosphate G protein-coupled receptors. Therefore, understanding the biology of this new class of receptors will be important in clarifying the immunological function of bioactive lysosphingolipid ligands. The S1P(4) receptor has generated interest due to its lymphoid tissue distribution. While the S1P(4) receptor binds the prototypical ligand, S1P, a survey of other lysosphingolipids demonstrated that 4D-hydroxysphinganine 1-phosphate, more commonly known as phytosphingosine 1-phosphate (PhS1P), binds to S1P(4) with higher affinity. Using radiolabeled S1P (S133P), the affinity of PhS1P for the S1P(4) receptor is 1.6nM, while that of S1P is nearly 50-fold lower (119+/-20nM). Radiolabeled PhS1P proved to be superior to S133P in routine binding assays due to improved signal-to-noise ratio. The present study demonstrates the utility of a novel radiolabeled probe, PhS133P, for in vitro studies of the S1P(4) receptor pharmacology.

  7. Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    PubMed

    Tsuji, Takashi; Suzuki, Keisuke; Nakamura, Tsuyoshi; Goto, Taiji; Sekiguchi, Yukiko; Ikeda, Takuya; Fukuda, Takeshi; Takemoto, Toshiyasu; Mizuno, Yumiko; Kimura, Takako; Kawase, Yumi; Nara, Futoshi; Kagari, Takashi; Shimozato, Takaichi; Yahara, Chizuko; Inaba, Shinichi; Honda, Tomohiro; Izumi, Takashi; Tamura, Masakazu; Nishi, Takahide

    2014-08-01

    We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.

  8. S1P lyase in skeletal muscle regeneration and satellite cell activation: exposing the hidden lyase.

    PubMed

    Saba, Julie D; de la Garza-Rodea, Anabel S

    2013-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid whose actions are essential for many physiological processes including angiogenesis, lymphocyte trafficking and development. In addition, S1P serves as a muscle trophic factor that enables efficient muscle regeneration. This is due in part to S1P's ability to activate quiescent muscle stem cells called satellite cells (SCs) that are needed for muscle repair. However, the molecular mechanism by which S1P activates SCs has not been well understood. Further, strategies for harnessing S1P signaling to recruit SCs for therapeutic benefit have been lacking. S1P is irreversibly catabolized by S1P lyase (SPL), a highly conserved enzyme that catalyzes the cleavage of S1P at carbon bond C(2-3), resulting in formation of hexadecenal and ethanolamine-phosphate. SPL enhances apoptosis through substrate- and product-dependent events, thereby regulating cellular responses to chemotherapy, radiation and ischemia. SPL is undetectable in resting murine skeletal muscle. However, we recently found that SPL is dynamically upregulated in skeletal muscle after injury. SPL upregulation occurred in the context of a tightly orchestrated genetic program that resulted in a transient S1P signal in response to muscle injury. S1P activated quiescent SCs via a sphingosine-1-phosphate receptor 2 (S1P2)/signal transducer and activator of transcription 3 (STAT3)-dependent pathway, thereby facilitating skeletal muscle regeneration. Mdx mice, which serve as a model for muscular dystrophy (MD), exhibited skeletal muscle SPL upregulation and S1P deficiency. Pharmacological SPL inhibition raised skeletal muscle S1P levels, enhanced SC recruitment and improved mdx skeletal muscle regeneration. These findings reveal how S1P can activate SCs and indicate that SPL suppression may provide a therapeutic strategy for myopathies. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.

  9. The Vicência meteorite fall: A new unshocked (S1) weakly metamorphosed (3.2) LL chondrite

    NASA Astrophysics Data System (ADS)

    Keil, Klaus; Zucolotto, Maria E.; Krot, Alexander N.; Doyle, Patricia M.; Telus, Myriam; Krot, Tatiana V.; Greenwood, Richard C.; Franchi, Ian A.; Wasson, John T.; Welten, Kees C.; Caffee, Marc W.; Sears, Derek W. G.; Riebe, My; Wieler, Rainer; Santos, Edivaldo; Scorzelli, Rosa B.; Gattacceca, Jerome; Lagroix, France; Laubenstein, Matthias; Mendes, Julio C.; Schmitt-Kopplin, Philippe; Harir, Mourad; Moutinho, Andre L. R.

    2015-06-01

    The Vicência meteorite, a stone of 1.547 kg, fell on September 21, 2013, at the village Borracha, near the city of Vicência, Pernambuco, Brazil. It was recovered immediately after the fall, and our consortium study showed it to be an unshocked (S1) LL3.2 ordinary chondrite. The LL group classification is based on the bulk density (3.13 g cm-3); the chondrule mean apparent diameter (0.9 mm); the bulk oxygen isotopic composition (δ17O = 3.768 ± 0.042‰, δ18O = 5.359 ± 0.042‰, Δ17O = 0.981 ± 0.020‰); the content of metallic Fe,Ni (1.8 vol%); the Co content of kamacite (1.73 wt%); the bulk contents of the siderophile elements Ir and Co versus Au; and the ratios of metallic Fe0/total iron (0.105) versus total Fe/Mg (1.164), and of Ni/Mg (0.057) versus total Fe/Mg. The petrologic type 3.2 classification is indicated by the beautifully developed chondritic texture, the standard deviation (~0.09) versus mean Cr2O3 content (~0.14 wt%) of ferroan olivine, the TL sensitivity and the peak temperature and peak width at half maximum, the cathodoluminescence properties of chondrules, the content of trapped 132Xetr (0.317 × 10-8cm3STP g-1), and the Raman spectra for organic material in the matrix. The cosmic ray exposure age is ~72 Ma, which is at the upper end of the age distribution of LL group chondrites. The meteorite is unusual in that it contains relatively large, up to nearly 100 μm in size, secondary fayalite grains, defined as olivine with Fa>75, large enough to allow in situ measurement of oxygen and Mn-Cr isotope systematics with SIMS. Its oxygen isotopes plot along a mass-dependent fractionation line with a slope of ~0.5 and Δ17O of 4.0 ± 0.3‰, and are similar to those of secondary fayalite and magnetite in the unequilibrated chondrites EET 90161, MET 96503, and Ngawi. These data suggest that secondary fayalite in Vicência was in equilibrium with a fluid with a Δ17O of ~4‰, consistent with the composition of the fluid in equilibrium with

  10. Ribosome-messenger recognition: mRNA target sites for ribosomal protein S1.

    PubMed Central

    Boni, I V; Isaeva, D M; Musychenko, M L; Tzareva, N V

    1991-01-01

    Ribosomal protein S1 is known to play an important role in translational initiation, being directly involved in recognition and binding of mRNAs by 30S ribosomal particles. Using a specially developed procedure based on efficient crosslinking of S1 to mRNA induced by UV irradiation, we have identified S1 binding sites on several phage RNAs in preinitiation complexes. Targets for S1 on Q beta and fr RNAs are localized upstream from the coat protein gene and contain oligo(U)-sequences. In the case of Q beta RNA, this S1 binding site overlaps the S-site for Q beta replicase and the site for S1 binding within a binary complex. It is reasonable that similar U-rich sequences represent S1 binding sites on bacterial mRNAs. To test this idea we have used E. coli ssb mRNA prepared in vitro with the T7 promoter/RNA polymerase system. By the methods of toeprinting, enzymatic footprinting, and UV crosslinking we have shown that binding of the ssb mRNA to 30S ribosomes is S1-dependent. The oligo(U)-sequence preceding the SD domain was found to be the target for S1. We propose that S1 binding sites, represented by pyrimidine-rich sequences upstream from the SD region, serve as determinants involved in recognition of mRNA by the ribosome. Images PMID:2011495

  11. Discovery of a novel series of potent S1P1 agonists.

    PubMed

    Crosignani, Stefano; Bombrun, Agnes; Covini, David; Maio, Maurizio; Marin, Delphine; Quattropani, Anna; Swinnen, Dominique; Simpson, Don; Sauer, Wolfgang; Françon, Bernard; Martin, Thierry; Cambet, Yves; Nichols, Anthony; Martinou, Isabelle; Burgat-Charvillon, Fabienne; Rivron, Delphine; Donini, Cristina; Schott, Olivier; Eligert, Valerie; Novo-Perez, Laurence; Vitte, Pierre-Alain; Arrighi, Jean-François

    2010-03-01

    The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.

  12. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development

    PubMed Central

    Jung, Bongnam; Obinata, Hideru; Galvani, Sylvain; Mendelson, Karen; Ding, Bisen; Skoura, Athanasia; Kinzel, Bernd; Brinkmann, Volker; Rafii, Shahin; Evans, Todd; Hla, Timothy

    2012-01-01

    SUMMARY During angiogenesis, nascent vascular sprouts fuse to form vascular networks enabling efficient circulation. Mechanisms that stabilize the vascular plexus are not well understood. Sphingosine 1-phosphate (S1P) is a blood-borne lipid mediator implicated in the regulation of vascular and immune systems. Here we describe a mechanism by which the G protein-coupled S1P receptor-1 (S1P1) stabilizes the primary vascular network. A gradient of S1P1 expression from the mature regions of the vascular network to the growing vascular front was observed. In the absence of endothelial S1P1, adherens junctions are destabilized, barrier function is breached, and flow is perturbed resulting in abnormal vascular hypersprouting. Interestingly, S1P1 responds to S1P as well as laminar shear stress to transduce flow-mediated signaling in endothelial cells both in vitro and in vivo. These data demonstrate that blood flow and circulating S1P activate endothelial S1P1 to stabilize blood vessels in development and homeostasis. PMID:22975328

  13. Intersystem crossing rates of S1 state keto-amino cytosine at low excess energy.

    PubMed

    Lobsiger, Simon; Etinski, Mihajlo; Blaser, Susan; Frey, Hans-Martin; Marian, Christel; Leutwyler, Samuel

    2015-12-21

    The amino-keto tautomer of supersonic jet-cooled cytosine undergoes intersystem crossing (ISC) from the v = 0 and low-lying vibronic levels of its S1((1)ππ(∗)) state. We investigate these ISC rates experimentally and theoretically as a function of S1 state vibrational excess energy Eexc. The S1 vibronic levels are pumped with a ∼5 ns UV laser, the S1 and triplet state ion signals are separated by prompt or delayed ionization with a second UV laser pulse. After correcting the raw ISC yields for the relative S1 and T1 ionization cross sections, we obtain energy dependent ISC quantum yields QISC (corr)=1%-5%. These are combined with previously measured vibronic state-specific decay rates, giving ISC rates kISC = 0.4-1.5 ⋅ 10(9) s(-1), the corresponding S1⇝S0 internal conversion (IC) rates are 30-100 times larger. Theoretical ISC rates are computed using SCS-CC2 methods, which predict rapid ISC from the S1; v = 0 state with kISC = 3 ⋅ 10(9) s(-1) to the T1((3)ππ(∗)) triplet state. The surprisingly high rate of this El Sayed-forbidden transition is caused by a substantial admixture of (1)nOπ(∗) character into the S1((1)ππ(∗)) wave function at its non-planar minimum geometry. The combination of experiment and theory implies that (1) below Eexc = 550 cm(-1) in the S1 state, S1⇝S0 internal conversion dominates the nonradiative decay with kIC ≥ 2 ⋅ 10(10) s(-1), (2) the calculated S1⇝T1 ((1)ππ(∗)⇝(3)ππ(∗)) ISC rate is in good agreement with experiment, (3) being El-Sayed forbidden, the S1⇝T1 ISC is moderately fast (kISC = 3 ⋅ 10(9) s(-1)), and not ultrafast, as claimed by other calculations, and (4) at Eexc ∼ 550 cm(-1) the IC rate increases by ∼50 times, probably by accessing the lowest conical intersection (the C5-twist CI) and thereby effectively switching off the ISC decay channels.

  14. S1P₁ localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity.

    PubMed

    Montrose, David C; Scherl, Ellen J; Bosworth, Brian P; Zhou, Xi Kathy; Jung, Bongnam; Dannenberg, Andrew J; Hla, Timothy

    2013-03-01

    Signaling through sphingosine-1-phosphate receptor₁ (S1P₁) promotes blood vessel barrier function. Degradation of S1P₁ results in increased vascular permeability in the lung and may explain side effects associated with administration of FTY720, a functional antagonist of the S1P₁ receptor that is currently used to treat multiple sclerosis. Ulcerative colitis (UC) is characterized by an increased density of abnormal vessels. The expression or role of S1P₁ in blood vessels in the colon has not been investigated. In the present study, we show that S1P₁ is overexpressed in the colonic mucosa of UC patients. This increase in S1P₁ levels reflects increased vascular density in the inflamed mucosa. Genetic deletion of S1pr1 in mice increases colonic vascular permeability under basal conditions and increases bleeding in experimental colitis. In contrast, neither FTY720 nor AUY954, two S1P receptor-targeting agents, increases bleeding in experimental colitis. Taken together, our findings demonstrate that S1P₁ is critical to maintaining colonic vascular integrity and may play a role in UC pathogenesis.

  15. S1←S0 vibronic spectra and structure of cyclopropanecarboxaldehyde molecule in the S1 lowest excited singlet electronic state

    NASA Astrophysics Data System (ADS)

    Godunov, I. A.; Yakovlev, N. N.; Terentiev, R. V.; Maslov, D. V.; Bataev, V. A.; Abramenkov, A. V.

    2016-11-01

    The S1←S0 vibronic spectra of gas-phase absorption at room temperature and fluorescence excitation of jet-cooled cyclopropanecarboxaldehyde (CPCA, c-C3H5CHO)were obtained and analyzed. In addition, the quantum chemical calculation (CASPT2/cc-pVTZ)was carried out for CPCA in the ground (S0) and lowest excited singlet (S1) electronic states. As a result, it was proved that the S1←S0 electronic excitation of the CPCA conformers (syn and anti) causes (after geometrical relaxation) significant structural changes, namely, the carbonyl fragments become non-planar and the cyclopropyl groups rotate around the central C-C bond. As a consequence, the potential energy surface of CPCA in the S1 state has six minima, 1ab, 2ab, and 3ab, corresponding to three pairs of mirror symmetry conformers: a and b. It was shown that vibronic bands of experimental spectra can be assigned to the 2(S1)←syn(S0) electronic transition with the origin at 30,481 cm-1. A number of fundamental vibrational frequencies for the 2 conformer of CPCA were assigned. In addition, several inversional energy levels for the 2 conformer were found and the 2a↔2b potential function of inversion was determined. The experimental barrier to inversion and the equilibrium angle between the CH bond and the CCO plane were calculated as 570 cm-1 and 28°, respectively.

  16. BaV3O8: A possible Majumdar-Ghosh system with S = (1)/(2)

    NASA Astrophysics Data System (ADS)

    Chakrabarty, T.; Mahajan, A. V.; Gippius, A. A.; Tkachev, A. V.; Büttgen, N.; Kraetschmer, W.

    2013-07-01

    BaV3O8 contains magnetic V4+(S=1/2) ions and also nonmagnetic V5+(S=0) ions. The V4+ ions are arranged in a coupled Majumdar-Ghosh chainlike network. A Curie-Weiss fit of our magnetic susceptibility χ(T) data in the temperature region of 80-300 K yields a Curie constant C=0.39 cm3K/mole V4+ and an antiferromagnetic Weiss temperature θ=-26K. The χ(T) curve shows a broad maximum at T≃25 K indicative of short-range order (SRO) and an anomaly corresponding to long-range order (LRO) at TN˜6 K. The value of the “frustration parameter” (f=|θ/TN|˜5) suggests that the system is moderately frustrated. Above the LRO temperature, the experimental magnetic susceptibility data match well with the coupled Majumdar-Ghosh (or Jnn-Jnnn Heisenberg) chain model with the ratio of the nnn (next-nearest neighbor) to nn (nearest neighbor) magnetic coupling α=2 and Jnnn/kB=40 K. In a mean-field approach when considering the interchain interactions, we obtain the total interchain coupling to be about 16 K. The LRO anomaly at TN is also observed in the specific heat CP(T) data and is not sensitive to an applied magnetic field up to 90 kOe. A 51V NMR signal corresponding to the nonmagnetic vanadium was observed. Anomalies at 6 K were observed in the variation with temperature of the 51V NMR linewidth and the spin-lattice relaxation rate 1/T1 indicating that they are sensitive to the LRO onset and fluctuations at the magnetic V sites. The existence of two components (one short and another long) is observed in the spin-spin relaxation rate 1/T2 data in the vicinity of TN. The shorter component seems to be intimately connected with the magnetically ordered state. We suggest that both magnetically ordered and nonlong-range-ordered (non-LRO) regions coexist in this compound below the long-range-ordering temperature.

  17. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    SciTech Connect

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    2011-09-09

    Highlights: {yields} Successfully selected specific PreS1-interacting peptides by using phage displayed library. {yields} Alignment of the positive phage clones revealed a consensus PreS1 binding motif. {yields} A highly enriched peptide named P7 had a strong binding ability for PreS1. {yields} P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX{sub n}HX{sub m}HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  18. Effects of α s1-casein (CSN1S1) and κ-casein (CSN3) genotypes on milk coagulation properties in Murciano-Granadina goats.

    PubMed

    Caravaca, Francisco; Ares, José Luis; Carrizosa, Juan; Urrutia, Baltasar; Baena, Francisca; Jordana, Jordi; Badaoui, Bouabid; Sànchez, Armand; Angiolillo, Antonella; Amills, Marcel; Serradilla, Juan Manuel

    2011-02-01

    The effects of the caprine α s1-casein (CSN1S1) polymorphisms on milk quality and cheese yield have been widely studied in French and Italian goat breeds. Much less is known about the consequences of κ-casein (CSN3) genotype on the technological and coagulation properties of goat milk. In the current study, we have performed an association analysis between polymorphisms at the goat CSN1S1 and CSN3 genes and milk coagulation (rennet coagulation time, curdling rate and curd firmness) and technological (time to cutting of curd and cheese yield) properties. In this analysis, we have included 193 records from 74 Murciano-Granadina goats (with genotypes constituted by different combinations of alleles B, E and F of the gene CSN1S1 and alleles A and B of the gene CSN3) distributed in three herds, which were collected bimonthly during a whole lactation. Data analysis, using a linear mixed model for repeated observations, revealed significant associations between CSN1S1 genotypes and the rate of the curdling process. In this way, milk from EE goats had a significantly higher curdling rate than milk from BB individuals (P<0·05). Contrary to previous experiments performed in French breeds, cheese yield was not significantly different in BB, EE and EF goats. Moreover, we have shown that CSN3 genotype has a significant effect on the rennet coagulation time (BB>AB, P<0·05) but not on cheese yield. No interaction between the CSN1S1 and CSN3 genotypes was observed.

  19. Pathophysiological Consequences of a Break in S1P1-Dependent Homeostasis of Vascular Permeability Revealed by S1P1 Competitive Antagonism

    PubMed Central

    Bigaud, Marc; Dincer, Zuhal; Bollbuck, Birgit; Dawson, Janet; Beckmann, Nicolau; Beerli, Christian; Fishli-Cavelti, Gina; Nahler, Michaela; Angst, Daniela; Janser, Philipp; Otto, Heike; Rosner, Elisabeth; Hersperger, Rene; Bruns, Christian; Quancard, Jean

    2016-01-01

    Rational Homeostasis of vascular barriers depends upon sphingosine 1-phosphate (S1P) signaling via the S1P1 receptor. Accordingly, S1P1 competitive antagonism is known to reduce vascular barrier integrity with still unclear pathophysiological consequences. This was explored in the present study using NIBR-0213, a potent and selective S1P1 competitive antagonist. Results NIBR-0213 was tolerated at the efficacious oral dose of 30 mg/kg BID in the rat adjuvant-induced arthritis (AiA) model, with no sign of labored breathing. However, it induced dose-dependent acute vascular pulmonary leakage and pleural effusion that fully resolved within 3–4 days, as evidenced by MRI monitoring. At the supra-maximal oral dose of 300 mg/kg QD, NIBR-0213 impaired lung function (with increased breathing rate and reduced tidal volume) within the first 24 hrs. Two weeks of NIBR-0213 oral dosing at 30, 100 and 300 mg/kg QD induced moderate pulmonary changes, characterized by alveolar wall thickening, macrophage accumulation, fibrosis, micro-hemorrhage, edema and necrosis. In addition to this picture of chronic inflammation, perivascular edema and myofiber degeneration observed in the heart were also indicative of vascular leakage and its consequences. Conclusions Overall, these observations suggest that, in the rat, the lung is the main target organ for the S1P1 competitive antagonism-induced acute vascular leakage, which appears first as transient and asymptomatic but could lead, upon chronic dosing, to lung remodeling with functional impairments. Hence, this not only raises the question of organ specificity in the homeostasis of vascular barriers, but also provides insight into the pre-clinical evaluation of a potential safety window for S1P1 competitive antagonists as drug candidates. PMID:28005953

  20. Synthesis and evaluation of CS-2100, a potent, orally active and S1P(3)- sparing S1P(1) agonist.

    PubMed

    Nakamura, Tsuyoshi; Asano, Masayoshi; Sekiguchi, Yukiko; Mizuno, Yumiko; Tamaki, Kazuhiko; Nara, Futoshi; Kawase, Yumi; Yabe, Yoshiyuki; Nakai, Daisuke; Kamiyama, Emi; Urasaki-Kaneno, Yoko; Shimozato, Takaichi; Doi-Komuro, Hiromi; Kagari, Takashi; Tomisato, Wataru; Inoue, Ryotaku; Nagasaki, Miyuki; Yuita, Hiroshi; Oguchi-Oshima, Keiko; Kaneko, Reina; Nishi, Takahide

    2012-05-01

    Modulators of sphingosine phosphate receptor-1 (S1P(1)) have recently been focused as a suppressant of autoimmunity. We have discovered a 4-ethylthiophene-based S1P(1) agonist 1-({4-Ethyl-5-[5-(4-phenoxyphenyl)-1,2,4-oxadiazol-3-yl]-2-thienyl}methyl)azetidine-3-carboxylic acid (CS-2100, 8) showing potent S1P(1) agonist activity against S1P(3) and an excellent in vivo potency. We report herein the synthesis of CS-2100 (8) and pharmacological effects such as S1P(1) and S1P(3) agonist activity in vitro, peripheral blood lymphocyte lowering effects and the suppressive effects on adjuvant-induced arthritis and experimental autoimmune encephalomyelitis (EAE) in animal models. The pharmacokinetic data were also reported. CS-2100 (8) had >5000-fold greater agonist activity for human S1P(1) (EC(50); 4.0 nM) relative to S1P(3) (EC(50); >20,000 nM). Following administration of single oral doses of 0.1 and 1 mg/kg of CS-2100 (8) in rats, lymphocyte counts decreased significantly, with a nadir at 8 and/or 12 h post-dose and recovery to vehicle control levels by 24-48 h post-dose. CS-2100 (8) is efficacious in the adjuvant-induced arthritis model in rats (ID(50); 0.44 mg/kg). In the EAE model compared to the vehicle-treated group, significant decreases in the cumulative EAE scores were observed for 0.3 and 1 mg/kg CS-2100 (8) groups in mice. While CS-2100 (8) showed potent efficacy in various animal disease models, it was also revealed that the central 1,2,4-oxadiazole ring of CS-2100 (8) was decomposed by enterobacteria in intestine of rats and monkeys, implicating the latent concern about an external susceptibility in its metabolic process in the upcoming clinical studies.

  1. To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient.

    PubMed

    Liu, Jingjing; Hsu, Andrew; Lee, Jen-Fu; Cramer, Daniel E; Lee, Menq-Jer

    2011-01-26

    Most hematopoietic stem progenitor cells (HSPCs) reside in bone marrow (BM), but a small amount of HSPCs have been found to circulate between BM and tissues through blood and lymph. Several lines of evidence suggest that sphingosine-1-phosphate (S1P) gradient triggers HSPC egression to blood circulation after mobilization from BM stem cell niches. Stem cells also visit certain tissues. After a temporary 36 h short stay in local tissues, HSPCs go to lymph in response to S1P gradient between lymph and tissue and eventually enter the blood circulation. S1P also has a role in the guidance of the primitive HSPCs homing to BM in vivo, as S1P analogue FTY720 treatment can improve HSPC BM homing and engraftment. In stress conditions, various stem cells or progenitor cells can be attracted to local injured tissues and participate in local tissue cell differentiation and tissue rebuilding through modulation the expression level of S1P(1), S1P(2) or S1P(3) receptors. Hence, S1P is important for stem cells circulation in blood system to accomplish its role in body surveillance and injury recovery.

  2. Mechanism of the S1 excited state internal conversion in vitamin B12.

    PubMed

    Lodowski, Piotr; Jaworska, Maria; Andruniów, Tadeusz; Garabato, Brady D; Kozlowski, Pawel M

    2014-09-21

    To explain the photostability of vitamin B12, internal conversion of the S1 state was investigated using TD-DFT. The active coordinates for radiationless deactivation were determined to be elongated axial bonds, overcoming a 5.0 kcal mol(-1) energy barrier between the relaxed ligand-to-metal charge transfer (S1), and the ground (S0) states.

  3. To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.

    PubMed

    Chew, Wee Siong; Wang, Wei; Herr, Deron R

    2016-11-01

    Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P1). In 2010, fingolimod became the first oral medication approved for the treatment of multiple sclerosis (MS). Since then, second-generation S1P receptor modulators have been under development in an effort to provide improved safety and efficacy profiles for MS, and to broaden their use to other autoimmune indications. Beyond the development of S1P1-modulators, there has been considerable effort in targeting other components of the S1P signaling pathway for the treatment of other diseases, such as cardiovascular disease, sepsis, and cancer. This manuscript provides an overview of the clinical and preclinical development of drugs targeting S1P signaling.

  4. Genome sequence of Bacillus pumilus S-1, an efficient isoeugenol-utilizing producer for natural vanillin.

    PubMed

    Su, Fei; Hua, Dongliang; Zhang, Zhaobin; Wang, Xiaoyu; Tang, Hongzhi; Tao, Fei; Tai, Cui; Wu, Qiulin; Wu, Geng; Xu, Ping

    2011-11-01

    Bacillus pumilus S-1 is an efficient isoeugenol-utilizing producer of natural vanillin. The genome of B. pumilus S-1 contains the epoxide hydrolase and six candidate monooxygenases that make it possible to explore the mechanism involved in conversion of isoenguenol to vanillin in the B. pumilus strain.

  5. VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST END OF QUARRY LOCK, FACING NORTHWEST - U.S. Naval Base, Pearl Harbor, Naval Submarine Base, Berthing Wharf S1, South Waterfront Road along north side of Quarry Loch, Pearl City, Honolulu County, HI

  6. Enhanced Raman scattering from cesium suboxides on silver particles and the structure of S-1 photocathodes

    NASA Technical Reports Server (NTRS)

    Bates, C. W., Jr.

    1984-01-01

    An explanation is given for the results of recent enhanced Raman scattering studies of photomultiplier tubes with S-1 photocathode surfaces which indicated the presence of Cs11O3 but not Cs2O. The reason for the discrepancy between the currently accepted model of the S-1 and this recent result is discussed.

  7. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury

    PubMed Central

    Liu, Huiying; Zhang, Zili; Li, Puyuan; Yuan, Xin; Zheng, Jing; Liu, Jinwen

    2016-01-01

    Background Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30–40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P. Methods By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. Results It was found that the down-regulation of TNF-α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. Discussions The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their

  8. Short communication: Carora cattle show high variability in alpha(s1)-casein.

    PubMed

    Caroli, A; Chessa, S; Chiatti, F; Rignanese, D; Meléndez, B; Rizzi, R; Ceriotti, G

    2008-01-01

    The objective of this study was to analyze the genetic variability of milk proteins of the Carora, a shorthorned Bos taurus cattle breed in Venezuela and in other Southern American countries that is primarily used for milk production. A total of 184 individual milk samples were collected from Carora cattle in 5 herds in Venezuela. The milk protein genes alpha(s1)-casein (CN) (CSN1S1), beta-CN (CSN2), kappa-CN (CSN3), and beta-lactoglobulin (LGB) were typed at the protein level by isoelectrofocusing. It was necessary to further analyze CSN1S1 at the DNA level by a PCR-based method to distinguish CSN1S1*G from B. Increased variation was found in particular at the CSN1S1 gene, where 4 variants were identified. The predominant variant was CSN1S1*B (frequency = 0.8). The second most common CSN1S1 variant was CSN1S1*G (0.101), followed by CSN1S1*C (0.082). Moreover, a new isoelectrofocusing pattern was identified, which may result from a novel CSN1S1 variant, named CSN1S1*I, migrating at an intermediate position between CSN1S1*B and CSN1S1*C. Six cows carried the variant at the heterozygous condition. For the other loci, predominance of CSN2*A2 (0.764), CSN3*B (0.609), and LGB*B (0.592) was observed. Haplotype frequencies (AF) at the CSN1S1-CSN2-CSN3 complex were also estimated by taking association into account. Only 7 haplotypes showed AF values >0.05, accounting for a cumulative frequency of 0.944. The predominant haplotype was B-A2-B (frequency = 0.418), followed by B-A2-A (0.213). The occurrence of the G variant is at a rather high frequency, which is of interest for selection within the Carora breed because of the negative association of this variant with the synthesis of the specific protein. From a cheese-making point of view, this variant is associated with improved milk-clotting parameters but is negatively associated with cheese ripening. Thus, milk protein typing should be routinely carried out in the breed, with particular emphasis on using a DNA test to

  9. Local Equivalence of Representations of {Diff^+(S^1)} Corresponding to Different Highest Weights

    NASA Astrophysics Data System (ADS)

    Weiner, Mihály

    2017-01-01

    Let c, h and {c,tilde{h}} be two admissible pairs of central charge and highest weight for {Diff^+(S^1)} . It is shown here that the positive energy irreducible projective unitary representations {U_{c,h}} and {U_{c,tilde{h}}} of the group {Diff^+(S^1)} are locally equivalent. This means that for any {ISubset S^1} open proper interval, there exists a unitary operator W I such that {W_I U_{c,h}(γ)W_I^* = U_{c,tilde{h}}(γ)} for all {γ in Diff^+(S^1)} which act identically on {I^c≡ S^1{setminus} I} (i.e., which can "displace" or "move" points only in I). This result extends and completes earlier ones that dealt with only certain regions of the "c, h-plane", and closes the gap in the full classification of superselection sectors of Virasoro nets.

  10. SUSY structures, representations and Peter-Weyl theorem for S 1 | 1

    NASA Astrophysics Data System (ADS)

    Carmeli, C.; Fioresi, R.; Kwok, S.

    2015-09-01

    The real compact supergroup S 1 | 1 is analysed from different perspectives and its representation theory is studied. We prove it is the only (up to isomorphism) supergroup, which is a real form of (C 1 | 1) × with reduced Lie group S1, and a link with SUSY structures on C 1 | 1 is established. We describe a large family of complex semisimple representations of S 1 | 1 and we show that any S 1 | 1-representation whose weights are all nonzero is a direct sum of members of our family. We also compute the matrix elements of the members of this family and we give a proof of the Peter-Weyl theorem for S 1 | 1.

  11. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for two years to equalize CSN1S1 and TG genetic marker frequencies to evaluate the epista...

  12. Phosphorylation of αS1-casein is regulated by different genes.

    PubMed

    Bijl, E; van Valenberg, H J F; Huppertz, T; van Hooijdonk, A C M; Bovenhuis, H

    2014-11-01

    Casein phosphorylation is a posttranslational modification catalyzed by kinase enzymes that attach phosphate groups to specific AA in the protein sequence. This modification is one of the key factors responsible for the stabilization of calcium phosphate nanoclusters in casein micelles and for the internal structure of the casein micelles. α(S1)-Casein (α(s1)-CN) is of special interest because it constitutes up to 40% of the total casein fraction in milk, and it has 2 common phosphorylation states, with 8 (α(S1)-CN-8P) and 9 (α(S1)-CN-9P) phosphorylated serine residues. Factors affecting this variation in the degree of phosphorylation are not currently known. The objective of this research was to determine the genetic background of α(S1)-CN-8P and α(S1)-CN-9P. The genetic and phenotypic correlation between α(S1)-CN-8P and α(S1)-CN-9P was low (0.18 and 0.19, respectively). This low genetic correlation suggests a different genetic background. These differences were further investigated by means of a genome-wide association study, which showed that both α(S1)-CN-8P and α(S1)-CN-9P were affected by a region on Bos taurus autosome (BTA) 6, but only α(S1)-CN-8P was affected by a region on BTA11 that contains the gene that encodes for β-lactoglobulin (β-LG), and only α(S1)-CN-9P was affected by a region on BTA14 that contains the diacylglycerol acyltransferase 1 (DGAT1) gene. Estimated effects of β-LG protein genotypes showed that only α(S1)-CN-8P was associated with the β-LG A/B polymorphism (g.1772G>A and g.3054C>T); the AA genotype of β-LG was associated with a lower concentration of α(S1)-CN-8P (-0.32% wt/wt) than the BB genotype (+0.41% wt/wt). Estimated effects of DGAT1 K232A genotypes showed that only α(S1)-CN-9P was associated with the DGAT1 gene polymorphism; DGAT1 AA genotype was associated with a higher α(S1)-CN-9P concentration (+0.53% wt/wt) than the DGAT1 KK genotype (-0.44% wt/wt). The results give insight in phosphorylation of α(S1

  13. One-stage surgery through posterior approach-for L5-S1 spondyloptosis

    PubMed Central

    Suslu, Hikmet Turan; Celikoglu, Erhan; Borekcı, Ali; Hıcdonmez, Tufan; Suslu, Hüsnü

    2011-01-01

    Grade 5 spondylolisthesis or spondyloptosis is a rare condition. Generally, the surgical management of spondyloptosis includes multi-staged procedures instead of one-staged procedures. One-stage treatment for spondyloptosis is very rare. A 15-year-old girl with L5-S1 spondyloptosis was admitted with severe low back pain. There was no history of trauma. The patient underwent L5 laminectomy, L5-S1 discectomy, resection of sacral dome, reduction, L3-L4-L5-S1 pedicular screw fixation, and interbody-posterolateral fusion through the posterior approach. The reduction was maintained with bilateral L5-S1 discectomy, resection of the sacral dome, and transpedicular instrumentation from L3 to S1. In this particular case, one-staged approach was adequate for the treatment of L5-S1 spondyloptosis. One-staged surgery using the posterior approach may be adequate for the treatment of L5-S1 spondyloptosis while avoiding the risks inherent in anterior approaches. PMID:23125496

  14. S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection.

    PubMed

    Li, Yaling; Xie, Peng; Sun, Minhua; Xiang, Bin; Kang, Yinfeng; Gao, Pei; Zhu, Wenxian; Ning, Zhangyong; Ren, Tao

    2016-01-01

    Newcastle disease virus (NDV) is the causative agent of Newcastle disease, which is characterized by inflammatory pathological changes in the organs of chickens. The inflammatory response to this disease has not been well characterized. Previous reports showed that the sphingosine-1-phosphate-1 receptor (S1PR1), a G protein-coupled receptor, is important to the activation of inflammatory responses. To understand better the viral pathogenesis and host inflammatory response, we analyzed S1PR1 expression during NDV infection. We observed a direct correlation between chicken embryo fibroblast (CEF) cellular inflammatory responses and S1PR1 expression. Virulent NDV-infected CEF cells also had elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-18). When S1PR1 was inhibited by using the specific antagonist W146, pro-inflammatory cytokine production declined. Overexpression of S1PR1 resulted in increased virus-induced IL-1β production. S1PR1 expression levels did not impact significantly NDV replication. These findings highlight the important role of S1PR1 in inflammatory responses in NDV infection.

  15. Identification of a pepducin acting as S1P3 receptor antagonist.

    PubMed

    Severino, Beatrice; Incisivo, Giuseppina Maria; Fiorino, Ferdinando; Bertolino, Antonio; Frecentese, Francesco; Barbato, Francesco; Manganelli, Serena; Maggioni, Giada; Capasso, Domenica; Caliendo, Giuseppe; Santagada, Vincenzo; Sorrentino, Raffaella; Roviezzo, Fiorentina; Perissutti, Elisa

    2013-11-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid with key functions in the immune, inflammatory, and cardiovascular systems. S1P exerts its action through the interaction with a family of five known G protein-coupled receptors, named S1P(1-5). Among them, S1P(3) has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. KRX-725 (compound 1) is a pepducin that mimics the effects of S1P by triggering specifically S1P(3). Here, aiming to identify novel S1P(3) antagonists, we carried out an alanine scanning analysis to address the contribution of the side chains of each amino acid residue to the peptide function. Then, deleted peptides from both the C- and N-terminus were prepared in order to determine the minimal sequence for activity and to identify the structural requirements for agonistic and, possibly, antagonistic behaviors. The pharmacological results of the Ala-scan derived compounds (2-10) suggested a high tolerance of the pepducin 1 to amino acid substitutions. Importantly, the deleted peptide 16 has the ability to inhibit, in a dose-dependent manner, both pepducin 1-induced vasorelaxation and fibroblast proliferation. Finally, a computational analysis was performed on the prepared compounds, showing that the supposed antagonists 16 and 17 appeared to be aligned with each other but not with the others. These results suggested a correlation between specific conformations and activities.

  16. 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene a novel compound isolated from Pycnocycla spinosa extract with potent anti-spasmodic and antidiarrheal properties

    PubMed Central

    Sadraei, H.; Ghanadian, M.; Asghari, G.; Sharifian, R.

    2015-01-01

    Bioassay monitoring of hydroalcoholic extract from the aerial part of Pyconcycla spinosa revealed that it contains components with spasmolytic activity in vitro. In addition, P. spinosa extract at oral dose of 1-5 mg/kg inhibits diarrhoea in animal models. Pharmacological screening of pure compounds isolated from P. spinosa hydroalcoholic extract led to the identification of 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (PABEM) which is a new diterpene. In this research, we have investigated antispasmodic and antidiarrheal effects of PABEM for comparison with P. spinosa extract. Aerial parts of P. spinosa were extracted with ethanol. For antispasmodic studies, rat isolated ileum was suspended in Tyrode's solution in an organ bath. The ileum was contracted by acetylcholine (ACh, 0.5 μM), serotonin (5-HT, 5 μM) or electrical field stimulation (EFS). P. spinosa extract in a concentration dependent manner (10-640 μg/ml) inhibited ileum contractions induced by ACh, 5-HT or EFS. The new compound isolated form P. spinosa extract “PABEM” in a similar manner inhibited the contractile response to ACh, 5-HT and EFS. However, the inhibitory effects of PABEM were observed at much lower bath concentrations. The relaxation effect of PABEM was started at 40 ng/ml bath concentration and with 2.5 μg/ml PABEM in the bath, the contractile responses of ileum were completely abolished. Both hydroalcoholic extract of P. spinosa and PABEM reduced intestinal meal transit and castor oil and MgSO4 induced diarrhoea in mice. However, PABEM was about 10 times more potent than its parent extract. This research shows that PABEM is probably the main component responsible for antispasmodic and antidiarrheal actions of P. spinosa extract. PMID:26430457

  17. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    SciTech Connect

    Kasamatsu, Atsushi; Uzawa, Katsuhiro; Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki; Endo-Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Takiguchi, Yuichi; Tanzawa, Hideki

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  18. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

    PubMed Central

    Santos-Cortez, Regie Lyn P.; Faridi, Rabia; Rehman, Atteeq U.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J.; Isaacson, Rivka; Belyantseva, Inna A.; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A.; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-e-Huma; Smith, Joshua D.; Nickerson, Deborah A.; Bamshad, Michael J.; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B.; Leal, Suzanne M.

    2016-01-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2−/− mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2−/− mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  19. Components-dependent optical nonlinearity in a series of CdSexS1-x and CdSexS1-x/ZnS QDs

    NASA Astrophysics Data System (ADS)

    Zhao, Shunlong; Wu, Feng; Zhang, Siwen; Wang, Qian; Li, Songtao; Cheng, Xiaoman

    2016-08-01

    The different compositions of the ternary alloyed CdSexS1-x and CdSexS1-x/ZnS core/shell quantum dots(CSQDs) have been synthesized by the chemical routes. The nonlinear optical properties of these QDs were investigated using Z-scan technique under the excitation of the 1064 nm picosecond laser pulse. The Z-scan results reveal that the nonlinear refractive indices of these QDs can be tuned by changing the ratio of Se and S components. Nonlinear optical (NLO) properties have been shown to be enhanced in CSQDs as compared to their core semiconductor counterparts. These QDs exhibit the components-tuned nonlinear refraction indices, which lead to a wide application in the photonic field.

  20. Heart Disease Could Cost U.S. $1 Trillion Per Year by 2035: Report

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_163587.html Heart Disease Could Cost U.S. $1 Trillion Per Year By ... estimates that nearly half of Americans will have heart disease in less than 20 years To use the ...

  1. Preparation of (S)-1-Halo-2-octanols Using Ionic Liquids and Biocatalysts.

    PubMed

    Oromí-Farrús, Mireia; Eras, Jordi; Sala, Núria; Torres, Mercè; Canela, Ramon

    2009-10-23

    Preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol was carried out by the enzymatic hydrolysis of halohydrin palmitates using biocatalysts. Halohydrin palmitates were prepared by various methods from palmitic acid and 1,2-octanediol. A tandem hydrolysis was carried out using lipases from Candida antarctica (Novozym 435), Rhizomucor miehei (Lipozyme IM), and "resting cells" from a Rhizopus oryzae strain that was not mycotoxigenic. The influence of the enzyme and the reaction medium on the selective hydrolysis of isomeric mixtures of halohydrin esters is described. Novozym 435 allowed preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol after 1-3 h of reaction at 40 degrees C in [BMIM][PF(6)].

  2. PMMA Cementoplasty in Symptomatic Metastatic Lesions of the S1 Vertebral Body

    SciTech Connect

    Dehdashti, Amir R.; Martin, Jean-Baptiste; Jean, Beatrix; Ruefenacht, Daniel A.

    2000-03-15

    We describe a lateral transiliac direct puncture approach to the S1 vertebral body for polymethylmethacrylate (PMMA) cementoplasty of painful metastatic lesions. This approach was performed using a 15-cm-long trocar needle with 3-mm outer diameter, introduced under general anesthesia and fluoroscopic control. A lateral projection was used to center the needle just in front of the spinal canal and subjacent to the superior plate of the S1 vertebral body. Needle progression was controlled using anteroposterior and lateral fluoroscopic projections alternately with a needle course parallel to an axial plane, avoiding conflict with the S1 foramen. After needle tip placement in the center of the S1 vertebral body, diluted PMMA with a setting time of 8 min was delivered. Ipsilateral lesions of the lateral sacral compartment were filled with the same needle by stepwise withdrawal and continuous PMMA injection.

  3. Second generation S1P pathway modulators: research strategies and clinical developments.

    PubMed

    Bigaud, Marc; Guerini, Danilo; Billich, Andreas; Bassilana, Frederic; Brinkmann, Volker

    2014-05-01

    Multiple Sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system (CNS) through demyelination and neurodegeneration. Until recently, major therapeutic treatments have relied on agents requiring injection delivery. In September 2010, fingolimod/FTY720 (Gilenya, Novartis) was approved as the first oral treatment for relapsing forms of MS. Fingolimod causes down-modulation of S1P1 receptors on lymphocytes which prevents the invasion of autoaggressive T cells into the CNS. In astrocytes, down-modulation of S1P1 by the drug reduces astrogliosis, a hallmark of MS, thereby allowing restoration of productive astrocyte communication with other neural cells and the blood brain barrier. Animal data further suggest that the drug directly supports the recovery of nerve conduction and remyelination. In human MS, such mechanisms may explain the significant decrease in the number of inflammatory markers on brain magnetic resonance imaging in recent clinical trials, and the reduction of brain atrophy by the drug. Fingolimod binds to 4 of the 5 known S1P receptor subtypes, and significant efforts were made over the past 5 years to develop next generation S1P receptor modulators and determine the minimal receptor selectivity needed for maximal therapeutic efficacy in MS patients. Other approaches considered were competitive antagonists of the S1P1 receptor, inhibitors of the S1P lyase to prevent S1P degradation, and anti-S1P antibodies. Below we discuss the current status of the field, and the functional properties of the most advanced compounds. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.

  4. Characterization of the L4-L5-S1 motion segment using the stepwise reduction method.

    PubMed

    Jaramillo, Héctor Enrique; Puttlitz, Christian M; McGilvray, Kirk; García, José J

    2016-05-03

    The two aims of this study were to generate data for a more accurate calibration of finite element models including the L5-S1 segment, and to find mechanical differences between the L4-L5 and L5-S1 segments. Then, the range of motion (ROM) and facet forces for the L4-S1 segment were measured using the stepwise reduction method. This consists of sequentially testing and reducing each segment in nine stages by cutting the ligaments, facet capsules, and removing the nucleus. Five L4-S1 human segments (median: 65 years, range: 53-84 years, SD=11.0 years) were loaded under a maximum pure moment of 8Nm. The ROM was measured using stereo-photogrammetry via tracking of three markers and the facet contact forces (CF) were measured using a Tekscan system. The ROM for the L4-L5 segment and all stages showed good agreement with published data. The major differences in ROM between the L4-L5 and L5-S1 segments were found for lateral bending and all stages, for which the L4-L5 ROM was about 1.5-3 times higher than that of the L5-S1 segment, consistent with L5-S1 facet CF about 1.3 to 4 times higher than those measured for the L4-L5 segment. For the other movements and few stages, the L4-L5 ROM was significantly lower that of the L5-S1 segment. ROM and CF provide important baseline data for more accurate calibration of FE models and to understand the role that their structures play in lower lumbar spine mechanics.

  5. Isolation of new Stenotrophomonas bacteriophages and genomic characterization of temperate phage S1.

    PubMed

    García, Pilar; Monjardín, Cristina; Martín, Rebeca; Madera, Carmen; Soberón, Nora; Garcia, Eva; Meana, Alvaro; Suárez, Juan E

    2008-12-01

    Twenty-two phages that infect Stenotrophomonas species were isolated through sewage enrichment and prophage induction. Of them, S1, S3, and S4 were selected due to their wide host ranges compared to those of the other phages. S1 and S4 are temperate siphoviruses, while S3 is a virulent myovirus. The genomes of S3 and S4, about 33 and 200 kb, were resistant to restriction digestion. The lytic cycles lasted 30 min for S3 and about 75 min for S1 and S4. The burst size for S3 was 100 virions/cell, while S1 and S4 produced about 75 virus particles/cell. The frequency of bacteriophage-insensitive host mutants, calculated by dividing the number of surviving colonies by the bacterial titer of a parallel, uninfected culture, ranged between 10(-5) and 10(-6) for S3 and 10(-3) and 10(-4) for S1 and S4. The 40,287-bp genome of S1 contains 48 open reading frames (ORFs) and 12-bp 5' protruding cohesive ends. By using a combination of bioinformatics and experimental evidence, functions were ascribed to 21 ORFs. The morphogenetic and lysis modules are well-conserved, but no lysis-lysogeny switch or DNA replication gene clusters were recognized. Two major clusters of genes with respect to transcriptional orientation were observed. Interspersed among them were lysogenic conversion genes encoding phosphoadenosine phosphosulfate reductase and GspM, a protein involved in the general secretion system II. The attP site of S1 may be located within a gene that presents over 75% homology to a Stenotrophomonas chromosomal determinant.

  6. SIRT1 mediates Sphk1/S1P-induced proliferation and migration of endothelial cells.

    PubMed

    Gao, Zhan; Wang, Hua; Xiao, Feng-Jun; Shi, Xue-Feng; Zhang, Yi-Kun; Xu, Qin Qin; Zhang, Xiao-Yan; Ha, Xiao-Qin; Wang, Li-Sheng

    2016-05-01

    Angiogenesis is one of the most important components of embryonic organ formation and vessel growth after birth. Sphingosine kinase 1 (Sphk1) and S1P has been confirmed to participate in various cell signaling pathways and physiological processes including neovascularisation. However, the mechanisms that Sphk1/S1P regulates neovascularisation remain unclear. In this study, we elucidated that Sphk1/S1P upregulates sirtuin 1 (SIRT1), a NAD+ dependent deacetylases protease which exerts multiple cellular functions, to regulate the proliferation and migration of endothelial cells. By using CCK8 and Transwell assays, we demonstrated that Sphk1 and SIRT1 knockdown could significantly decrease proliferation and migration of HUVEC cells. Sphk1 inhibition results in SIRT1 downregulation which could be reversed by exogenous S1P in HUVEC cells. Treatment of HUVECs with S1P reverses the impaired proliferation and migration caused by SIRT1 knockdown. Furthermore, Sphk1 knockdown inhibits the phosphorylation of P38 MAPK, ERK and AKT. Treatment of HUVECs with PD98059, SB203580 and Wortmannin, which are the inhibitors of ERK, P38 MAPK and AKT respectively, resulted in decreased SIRT1 expression and reduced migration of HUVEC cells. Thus, we conclude that Sphk1/S1P induces SIRT1 upregulation through multiple pathways including P38 MAPK, ERK and AKT signals. This is the first report to disclose the existence and roles of Sphk1/S1P/SIRT1 axis in regulation of endothelial cell proliferation and migration, which may provide a theoretical basis for angiogenesis.

  7. The Effects of Spinopelvic Parameters and Paraspinal Muscle Degeneration on S1 Screw Loosening

    PubMed Central

    Kim, Jin-Bum; Lee, Young-Seok; Nam, Taek-Kyun; Park, Yong-Sook; Kim, Young-Baeg

    2015-01-01

    Objective To investigate risk factors for S1 screw loosening after lumbosacral fusion, including spinopelvic parameters and paraspinal muscles. Methods We studied with 156 patients with degenerative lumbar disease who underwent lumbosacral interbody fusion and pedicle screw fixation including the level of L5-S1 between 2005 and 2012. The patients were divided into loosening and non-loosening groups. Screw loosening was defined as a halo sign larger than 1 mm around a screw. We checked cross sectional area of paraspinal muscles, mean signal intensity of the muscles on T2 weight MRI as a degree of fatty degeneration, spinopelvic parameters, bone mineral density, number of fusion level, and the characteristic of S1 screw. Results Twenty seven patients showed S1 screw loosening, which is 24.4% of total. The mean duration for S1 screw loosening was 7.3±4.1 months after surgery. Statistically significant risk factors were increased age, poor BMD, 3 or more fusion levels (p<0.05). Among spinopelvic parameters, a high pelvic incidence (p<0.01), a greater difference between pelvic incidence and lumbar lordotic angle preoperatively (p<0.01) and postoperatively (p<0.05). Smaller cross-sectional area and high T2 signal intensity in both multifidus and erector spinae muscles were also significant muscular risk factors (p<0.05). Small converging angle (p<0.001) and short intraosseous length (p<0.05) of S1 screw were significant screw related risk factors (p<0.05). Conclusion In addition to well known risk factors, spinopelvic parameters and the degeneration of paraspinal muscles also showed significant effects on the S1 screw loosening. PMID:26587190

  8. Effects of S1P on skeletal muscle repair/regeneration during eccentric contraction.

    PubMed

    Sassoli, Chiara; Formigli, Lucia; Bini, Francesca; Tani, Alessia; Squecco, Roberta; Battistini, Chiara; Zecchi-Orlandini, Sandra; Francini, Fabio; Meacci, Elisabetta

    2011-11-01

    Skeletal muscle regeneration is severely compromised in the case of extended damage. The current challenge is to find factors capable of limiting muscle degeneration and/or potentiating the inherent regenerative program mediated by a specific type of myoblastic cells, the satellite cells. Recent studies from our groups and others have shown that the bioactive lipid, sphingosine 1-phosphate (S1P), promotes myoblast differentiation and exerts a trophic action on denervated skeletal muscle fibres. In the present study, we examined the effects of S1P on eccentric contraction (EC)-injured extensor digitorum longus muscle fibres and resident satellite cells. After EC, skeletal muscle showed evidence of structural and biochemical damage along with significant electrophysiological changes, i.e. reduced plasma membrane resistance and resting membrane potential and altered Na(+) and Ca(2+) current amplitude and kinetics. Treatment with exogenous S1P attenuated the EC-induced tissue damage, protecting skeletal muscle fibre from apoptosis, preserving satellite cell viability and affecting extracellular matrix remodelling, through the up-regulation of matrix metalloproteinase 9 (MMP-9) expression. S1P also promoted satellite cell renewal and differentiation in the damaged muscle. Notably, EC was associated with the activation of sphingosine kinase 1 (SphK1) and with increased endogenous S1P synthesis, further stressing the relevance of S1P in skeletal muscle protection and repair/regeneration. In line with this, the treatment with a selective SphK1 inhibitor during EC, caused an exacerbation of the muscle damage and attenuated MMP-9 expression. Together, these findings are in favour for a role of S1P in skeletal muscle healing and offer new clues for the identification of novel therapeutic approaches to counteract skeletal muscle damage and disease.

  9. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P{sub 2} on cell migration and invasiveness

    SciTech Connect

    Young, Nicholas; Van Brocklyn, James R. . E-mail: james.vanbrocklyn@osumc.edu

    2007-05-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P{sub 1-5}. S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P{sub 1}, S1P{sub 2} and S1P{sub 3} all contribute positively to S1P-stimulated glioma cell proliferation, with S1P{sub 1} being the major contributor. Stimulation of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P{sub 5} blocks glioma cell proliferation, and inhibits ERK activation. S1P{sub 1} and S1P{sub 3} enhance glioma cell migration and invasion. S1P{sub 2} inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P{sub 2} also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P{sub 2}-stimulated glioma invasion. Thus, while S1P{sub 2} decreases glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix.

  10. Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial

    PubMed Central

    Zhou, Zun-Qiang; Guan, Jiao; Tong, Da-Nian; Zhou, Guang-Wen

    2016-01-01

    Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50–0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27–0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9<466 U/ml were more responsive to chemotherapeutic agents than those with CA19-9≥571 U/ml (88.9% vs 0%, P<0.001). We conclude that the combination of GEM plus S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733). PMID:27058753

  11. Arthrodesis to L5 versus S1 in long instrumentation and fusion for degenerative lumbar scoliosis.

    PubMed

    Cho, Kyu-Jung; Suk, Se-Il; Park, Seung-Rim; Kim, Jin-Hyok; Choi, Sung-Wook; Yoon, Young-Hyun; Won, Man-Hee

    2009-04-01

    There is a debate regarding the distal fusion level for degenerative lumbar scoliosis. Whether a healthy L5-S1 motion segment should be included or not in the fusion remains controversial. The purpose of this study was to determine the optimal indication for the fusion to the sacrum, and to compare the results of distal fusion to L5 versus the sacrum in the long instrumented fusion for degenerative lumbar scoliosis. A total of 45 patients who had undergone long instrumentation and fusion for degenerative lumbar scoliosis were evaluated with a minimum 2 year follow-up. Twenty-four patients (mean age 63.6) underwent fusion to L5 and 21 patients (mean age 65.6) underwent fusion to the sacrum. Supplemental interbody fusion was performed in 12 patients in the L5 group and eleven patients in the sacrum group. The number of levels fused was 6.08 segments (range 4-8) in the L5 group and 6.09 (range 4-9) in the sacrum group. Intraoperative blood loss (2,754 ml versus 2,938 ml) and operative time (220 min versus 229 min) were similar in both groups. The Cobb angle changed from 24.7 degrees before surgery to 6.8 degrees after surgery in the L5 group, and from 22.8 degrees to 7.7 degrees in the sacrum group without statistical difference. Correction of lumbar lordosis was statistically better in the sacrum group (P = 0.03). Less correction of lumbar lordosis in the L5 group seemed to be associated with subsequent advanced L5-S1 disc degeneration. The change of coronal and sagittal imbalance was not different in both groups. Subsequent advanced L5-S1 disc degeneration occurred in 58% of the patients in the L5 group. Symptomatic adjacent segment disease at L5-S1 developed in five patients. Interestingly, the development of adjacent segment disease was not related to the preoperative grade of disc degeneration, which proved minimal degeneration in the five patients. In the L5 group, there were nine patients of complications at L5-S1 segment, including adjacent segment disease at

  12. Improvement of intratumor microdistribution of PEGylated liposome via tumor priming by metronomic S-1 dosing

    PubMed Central

    Doi, Yusuke; Abu Lila, Amr S; Matsumoto, Haruna; Okada, Tomoko; Shimizu, Taro; Ishida, Tatsuhiro

    2016-01-01

    The efficient delivery of nanocarrier-based cancer therapeutics into tumor tissue is problematic. Structural abnormalities, tumor vasculature heterogeneity, and elevated intratumor pressure impose barriers against the preferential accumulation of nanocarrier-based cancer therapeutics within tumor tissues and, consequently, compromise their therapeutic efficacy. Recently, we have reported that metronomic S-1, orally available tegafur formulation, dosing synergistically augmented the therapeutic efficacy of oxaliplatin (l-OHP)-containing PEGylated liposome without increasing the toxicity in animal model. However, the exact mechanism behind such synergistic effect was not fully elucidated. In this study, therefore, we tried to shed the light on the contributions of metronomic S-1 dosing to the enhanced accumulation and/or spatial distribution of PEGylated liposome within tumor tissue. Tumor priming with metronomic S-1 treatment induced a potent apoptotic response against both angiogenic endothelial cells and tumor cells adjacent to tumor blood vessels, resulting in enhanced tumor blood flow via transient normalization of tumor vasculature, along with alleviation of intratumor pressure. Such a change in the tumor microenvironment imparted by S-1 treatment allows efficient delivery of PEGylated liposome to tumor tissue and permits their deep penetration/distribution into the tumor mass. Such a priming effect of S-1 dosing can be exploited as a promising strategy to enhance the therapeutic efficacy of nanocarrier-based cancer therapeutics suffering from inadequate/heterogeneous delivery to tumor tissues. PMID:27822036

  13. Ultrasound and electrical nerve stimulation-guided S1 nerve root block.

    PubMed

    Sato, Masaki; Mikawa, Yasuhito; Matuda, Akiko

    2013-10-01

    A selective lumbosacral nerve root block is generally is performed under X-ray fluoroscopy, which has the disadvantage of radiation exposure and the need for fluoroscopy equipment. In this study, we assessed the effectiveness of ultrasound and nerve stimulation-guided S1 nerve root block on 37 patients with S1 radicular syndrome. With the patient in a prone position, an ultrasound scan was performed by placing the probe parallel to the body axis. The needle was pointed slightly medial from the lateral side of the probe and advanced toward a hyperechoic area in the sacral foramina with ultrasound guidance. Contrast medium was then injected and its dispersion confirmed by fluoroscopy. The acquired contrast images were classified into intraneural, perineural, and paraneural patterns. The significance of differences in the effect of the block among the contrast image patterns was analyzed. After nerve block, decreased sensation at the S1 innervated region and pain relief was achieved in all patients. No significant difference was noted in the effect of the block between perineural and paraneural patterns. In conclusion, this technique provided reliable S1 nerve root block in patients with S1 radicular syndrome and minimized radiation exposure.

  14. Far-ultraviolet Observations of Comet C/2012 S1 (ISON) from FORTIS

    NASA Astrophysics Data System (ADS)

    McCandliss, Stephan R.; Feldman, Paul D.; Weaver, Harold; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, S. Harvey

    2016-09-01

    We have used the unique far-UV imaging capability offered by a sounding-rocket-borne instrument to acquire observations of C/2012 S1 (ISON) when its angular separation with respect to the Sun was 26.°3 on 2013 November 20.49. At the time of observation, the comet’s heliocentric distance and velocity relative to the Sun were r h = 0.43 au and {\\dot{r}}h = -62.7 km s-1. Images dominated by C i λ1657 and H i λ1216 were acquired over a 106 × 106 km2 region. The water production rate implied by the Lyα observations is constrained to be {Q}{{{H}}2{{O}}}≈ 8 × 1029 s-1 while the neutral carbon production rate was {Q}C ≈ 4 ×1028 s-1. The radial profile of C i was consistent with it being a dissociation product of a parent molecule with a lifetime τ ˜ 5 × 104 s, favoring a parent other than CO. We constrain the Q CO production rate to {5}-7.5+1.5 × 1028 s-1 with 1σ errors derived from photon statistics. The upper limit on the Q CO/{Q}{{{H}}2{{O}}} is ≲6%.

  15. Corneal Limbal Stem Cell Deficiency Associated with the Anticancer Drug S-1

    PubMed Central

    Kim, Kyeong Hwan; Kim, Wan Soo

    2015-01-01

    ABSTRACT Purpose An oral antineoplastic drug, S-1, is known to be more effective with less toxicity and fewer gastrointestinal side effects than the conventional intravenous 5-fluorouracil. We report a case of limbal stem cell deficiency that occurred in a patient receiving chemotherapy using S-1 alone for gastric cancer. Case Report A 65-year-old woman with symptoms of grittiness and epiphora in both eyes for several months was referred to the ophthalmology clinic. She had been receiving S-1 orally after total gastrectomy for advanced gastric cancer. Slit lamp examination revealed an irregular hazy corneal epithelium in both eyes that extended to the center of the cornea overlying the pupil and showed late staining with fluorescein dye. Palisades of Vogt at the superior limbus were absent in both eyes. Best-corrected distance vision was 20/50 in both eyes with all other structures of the anterior and posterior segment unremarkable including a patent lacrimal drainage system. There was no change in the corneal lesions of either eye despite 3 months of topical therapy. The lesions did resolve in 4 months after discontinuation of S-1 therapy owing to acute renal failure. Conclusions Early detection of this adverse reaction before significant visual loss through regular follow-up appears to be important in patients receiving S-1 therapy. PMID:25756340

  16. PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

    PubMed

    Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2013-11-01

    We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells.

  17. Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways.

    PubMed

    Yoon, Chang Min; Hong, Bok Sil; Moon, Hyung Geun; Lim, Seyoung; Suh, Pann-Ghill; Kim, Yoon-Keun; Chae, Chi-Bom; Gho, Yong Song

    2008-08-15

    The lymphatic system plays pivotal roles in mediating tissue fluid homeostasis and immunity, and excessive lymphatic vessel formation is implicated in many pathological conditions, which include inflammation and tumor metastasis. However, the molecular mechanisms that regulate lymphatic vessel formation remain poorly characterized. Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that is implicated in a variety of biologic processes such as inflammatory responses and angiogenesis. Here, we first report that S1P acts as a lymphangiogenic mediator. S1P induced migration, capillary-like tube formation, and intracellular Ca(2+) mobilization, but not proliferation, in human lymphatic endothelial cells (HLECs) in vitro. Moreover, a Matrigel plug assay demonstrated that S1P promoted the outgrowth of new lymphatic vessels in vivo. HLECs expressed S1P1 and S1P3, and both RNA interference-mediated down-regulation of S1P1 and an S1P1 antagonist significantly blocked S1P-mediated lymphangiogenesis. Furthermore, pertussis toxin, U73122, and BAPTA-AM efficiently blocked S1P-induced in vitro lymphangiogenesis and intracellular Ca(2+) mobilization of HLECs, indicating that S1P promotes lymphangiogenesis by stimulating S1P1/G(i)/phospholipase C/Ca(2+) signaling pathways. Our results suggest that S1P is the first lymphangiogenic bioactive lipid to be identified, and that S1P and its receptors might serve as new therapeutic targets against inflammatory diseases and lymphatic metastasis in tumors.

  18. [A Case of Local Recurrence of Bile Duct Cancer Completely Responding to Chemoradiotherapy with S-1].

    PubMed

    Yamamichi, Keigo; Sueyoshi, Hiroyuki; Tanaka, Yoshito; Sakaguchi, Tatsuma; Hishikawa, Hidehiko; Ueda, Aiko; Matsuura, Takashi; Ozaki, Takashi; Saito, Takuya

    2015-11-01

    An 80-year-old man with common bile duct cancer was treated by pancreaticoduodenectomy with D2 lymph node dissection in October 2005. The patient presented with frequent episodes of bloody-mucous rectal discharge in July 2009. An abdominal CT demonstrated local recurrence at the hepatoduodenal ligament. We treated him with concurrent chemoradiotherapy (CRT) with single-dose S-1 chemotherapy. After 6 months, we diagnosed a complete response (CR) by follow-up CT. The patient was treated with S-1 for 3 years after the diagnosis of a CR. He is alive without disease 6 years after the diagnosis of the recurrence. Concurrent CRT with S-1 chemotherapy may be the therapy of choice for recurrence of bile duct cancer.

  19. The 2(2S + 1)-formalism and its connection with other descriptions

    NASA Astrophysics Data System (ADS)

    Dvoeglazov, Valeriy V.

    2016-02-01

    In the framework of the Joos-Weinberg 2(2S + 1)-theory for massless particles, the dynamical invariants have been derived from the Lagrangian density which is considered to be a 4-vector. A la Majorana interpretation of the 6-component “spinors”, the field operators of S = 1 particles, as the left- and right-circularly polarized radiation, leads us to the conserved quantities which are analogous to those obtained by Lipkin and Sudbery. The scalar Lagrangian of the Joos-Weinberg theory is shown to be equivalent to the Lagrangian of a free massless field, introduced by Hayashi. As a consequence of a new “gauge” invariance this skew-symmetric field describes physical particles with the longitudinal components only. The interaction of the spinor field with the Weinberg’s 2(2S + 1)-component massless field is considered. New interpretation of the Weinberg field function is proposed.

  20. Molecular and immunological characterisation of the glycosylated orange allergen Cit s 1

    PubMed Central

    Pöltl, Gerald; Ahrazem, Oussama; Paschinger, Katharina; Ibañez, M. Dolores; Salcedo, Gabriel; Wilson, Iain B. H.

    2010-01-01

    The IgE of sera from patients with a history of allergy to oranges (Citrus sinensis) bind a number of proteins in orange extract, including Cit s 1, a germin-like protein. In the present study, we have analysed its immunological cross-reactivity and its molecular nature. Sera from many of the patients examined recognise a range of glycoproteins and neoglycoconjugates containing β1,2-xylose and core α1,3-fucose on their N-glycans. These reagents also inhibited the interaction of Cit s 1 with patients’ sera, thus underlining the critical role of glycosylation in the recognition of this protein by patients’ IgE and extending previous data showing that deglycosylated Cit s 1 does not possess IgE epitopes. In parallel, we examined the peptide sequence and glycan structure of Cit s 1 using mass spectrometric techniques. Indeed, we achieved complete sequence coverage of the mature protein as compared to the translation of an expressed sequence tag cDNA clone and demonstrated that the single N-glycosylation site of this protein carries oligosaccharides with xylose and fucose residues. Due to the presumed requirement for multivalency for in vivo allergenicity, our molecular data showing that Cit s 1 is monovalent as regards glycosylation and that the single N-glycan is the target of the IgE response to this protein, therefore, explain the immunological cross-reactive properties of Cit s 1 as well as its equivocal nature as a clinically-relevant allergen. PMID:17095532

  1. Doubled haploid versus S1 family recurrent selection for testcross performance in a maize population.

    PubMed

    Bordes, J; Charmet, G; de Vaulx, R Dumas; Pollacsek, M; Beckert, M; Gallais, A

    2006-04-01

    Theoretically, in a recurrent selection program, the use of doubled haploids (DH) can increase genetic advance per unit of time. To evaluate the efficiency expected from the use of DH for the improvement of grain yield in a maize (Zea mays L.) population, two recurrent selection programs for testcross performance were initiated using testcross progenies from DH lines and S1 families. In 4 years one selection cycle using DH and two selection cycles using S1 families were carried out with the same selection intensity for both methods. As expected, testcross genetic variance was twice as high among DH lines as among S1 families. The predicted genetic gain was 8.2% for the DH selection cycle, and 10.6% for the two S1 selection cycles, giving a per year advantage of 29% for the S1 family method over the DH method with a cycle of 4 years. With a 3-year cycle for the DH method, both methods were expected to be equivalent. Using a tester related to the one used for selection, the genetic gains obtained were equivalent for both methods: 6.6% for the DH cycle and 7.0% for the two S1 cycles. With a 3-year cycle for the DH method, the advantage would have been in favor of DH method. Furthermore, the DH method has the advantage of simultaneously producing lines that are directly usable as parents of a hybrid. Thus, if the genetic advance per unit of time is evaluated at the level of developed varieties even with the same or with a lower genetic advance in population improvement, the DH method appears to be the most efficient.

  2. 11-cis retinal torsion: A QTAIM and stress tensor analysis of the S1 excited state

    NASA Astrophysics Data System (ADS)

    Maza, Julio R.; Jenkins, Samantha; Kirk, Steven R.

    2016-05-01

    We investigate torsion about the C11-C12 bond mid-point for the S1 state of 11-cis retinal, using a QTAIM and stress tensor analysis. The QTAIM and stress tensor responses to a torsion ±α increase at a faster rate for the preferred direction of torsion though the CI seam. A QTAIM and stress tensor vector-based analysis provides an alternative way of characterising the asymmetry of the S1 potential energy surface. In the vicinity of the CI seam the ellipticity ε attained minimum values. The application of this analysis to molecular rotary motors is briefly discussed.

  3. Biochemical regulation of breast cancer cell expression of S1P2 (Edg-5) and S1P3 (Edg-3) G protein-coupled receptors for sphingosine 1-phosphate.

    PubMed

    Dolezalova, Hana; Shankar, Geetha; Huang, Mei-Chuan; Bikle, Daniel D; Goetzl, Edward J

    2003-03-01

    G protein-coupled receptors (GPCRs) for lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) transduce signals to many functions of normal cells. Most human cancer cells upregulate S1P and LPA GPCRs, in patterns distinctive for each type of tumor. The findings that 1-alpha, 25-dihydroxy-vitamin D(3) (VD3) and all-trans retinoic acid (RA) differentially alter expression of the predominant S1P(3) (Edg-3) R and S1P(2) (Edg-5) R in human breast cancer cells (BCCs) permitted analyses of their individual activities, despite a lack of selective pharmacological probes. S1P-evoked increases in [Ca(2+)](i) in S1P(3) R-predominant BCCs were suppressed by concentrations of VD3 and RA which decreased expression of S1P(3) Rs, despite RA-induced increases in S1P(2) Rs. S1P-elicited chemokinetic migration of S1P(3) R-predominant BCCs across a type IV collagen-coated micropore filter also was inhibited by concentrations of VD3 and RA which decreased expression of S1P(3) Rs. The RA-induced increase in expression of S1P(2) Rs did not prevent suppression by RA of S1P-elicited chemokinesis, which appears to be mediated by S1P(3) Rs, but instead exposed S1P(2) R-mediated inhibition of epidermal growth factor-stimulated chemotaxis of BCCs. In contrast, expression of the predominant LPA(2) Rs, LPA-evoked increase in [Ca(2+)](i) and LPA-stimulated chemokinetic migration were suppressed concomitantly by RA but not VD3. Thus two structurally-homologous S1P Rs of BCCs differ in coupling to [Ca(2+)](i) signaling and have opposite effects on protein growth factor-stimulated chemotaxis.

  4. Effect of Self-Regulated Learning and Motivation to Achieve against Teacher Professional Capability for Student S1 PGSD of Science Field Compared with Regular Student S1 PGSD at UPBJJ Serang

    ERIC Educational Resources Information Center

    Prayekti

    2015-01-01

    This study is to know effect of self-regulated learning and motivation to achieve against teacher professional capability for student S1 PGSD of science field compared with regular student S1 PGSD. The student uses grades of Classroom Action Research (CAR) and Stabilization of Professional Capability (SPC) on curriculum of S1 PGSD to see…

  5. Molecular basis of reovirus virulence: Role of the S1 gene

    PubMed Central

    Weiner, Howard L.; Drayna, Dennis; Averill, Damon R.; Fields, Bernard N.

    1977-01-01

    A genetic approach has been used to define the molecular basis for the different patterns of virulence and central nervous system cell tropism exhibited by reovirus types 1 and 3. Intracerebral inoculation of reovirus type 3 into newborn mice causes a necrotizing encephalitis (without ependymal damage) that is uniformly fatal. Animal inoculated with reovirus type 1 generally survive and may develop epedymal cell damage (without neuronal necrosis) and hydrocephalus. Using recombinant clones derived from crosses between reovirus types 1 and 3, we have been able to determine that the S1 genome segment is responsible for the differing cell tropism of reovirus serotypes and is the major determinant of neurovirulence. The type 1 S1 genome segment is responsible for ependymal damage with subsequent hydrocephalus; the type 3 S1 genome segment is responsible for neuronal necrosis and neurovirulence. We postulate that these differences are due to the specific interaction of the σ1 outer capsid polypeptide (the protein coded for by the S1 genome segment) with receptors on the surface of either ependymal cells or neuronal cells. Images PMID:271999

  6. SKI-1/S1P inhibitor PF-429242 impairs the onset of HCV infection.

    PubMed

    Blanchet, Matthieu; Sureau, Camille; Guévin, Carl; Seidah, Nabil G; Labonté, Patrick

    2015-03-01

    Worldwide, approximately 170 million individuals are afflicted with chronic hepatitis C virus (HCV) infection. To prevent the development of inherent diseases such as cirrhosis and hepatocellular carcinoma, tremendous efforts have been made, leading to the development of promising new treatments. However, their efficiency is still dependent on the viral genotype. Additionally, these treatments that target the virus directly can trigger the emergence of resistant variants. In a previous study, we have demonstrated that a long-term (72h) inhibition of SKI-1/S1P, a master lipogenic pathway regulator through activation of SREBP, resulted in impaired HCV genome replication and infectious virion secretion. In the present study, we sought to investigate the antiviral effect of the SKI-1/S1P small molecule inhibitor PF-429242 at the early steps of the HCV lifecycle. Our results indicate a very potent antiviral effect of the inhibitor early in the viral lifecycle and that the overall action of the compound relies on two different contributions. The first one is SREBP/SKI-1/S1P dependent and involves LDLR and NPC1L1 proteins, while the second one is SREBP independent. Overall, our study confirms that SKI-1/S1P is a relevant target to impair HCV infection and that PF-429242 could be a promising candidate in the field of HCV infection treatment.

  7. Universality of the Ising and the S=1 model on Archimedean lattices: a Monte Carlo determination.

    PubMed

    Malakis, A; Gulpinar, G; Karaaslan, Y; Papakonstantinou, T; Aslan, G

    2012-03-01

    The Ising models S=1/2 and S=1 are studied by efficient Monte Carlo schemes on the (3,4,6,4) and the (3,3,3,3,6) Archimedean lattices. The algorithms used, a hybrid Metropolis-Wolff algorithm and a parallel tempering protocol, are briefly described and compared with the simple Metropolis algorithm. Accurate Monte Carlo data are produced at the exact critical temperatures of the Ising model for these lattices. Their finite-size analysis provide, with high accuracy, all critical exponents which, as expected, are the same with the well-known 2D Ising model exact values. A detailed finite-size scaling analysis of our Monte Carlo data for the S=1 model on the same lattices provides very clear evidence that this model obeys, also very well, the 2D Ising model critical exponents. As a result, we find that recent Monte Carlo simulations and attempts to define effective dimensionality for the S=1 model on these lattices are misleading. Accurate estimates are obtained for the critical amplitudes of the logarithmic expansions of the specific heat for both models on the two Archimedean lattices.

  8. Crystallization and preliminary crystallographic study of the yeast Malassezia sympodialis allergen Mala s 1

    SciTech Connect

    Vilhelmsson, Monica; Hallberg, B. Martin; Rasool, Omid; Zargari, Arezou; Scheynius, Annika; Achour, Adnane

    2006-02-01

    Crystals of the M. sympodialis allergen Mala s 1 have been obtained using the hanging-drop vapour-diffusion method. A diffraction data set has been collected from native crystals to 1.35 Å resolution. The opportunistic yeast Malassezia sympodialis can act as an allergen and elicit specific IgE- and T-cell reactivity in patients with atopic eczema. The first identified major allergen from M. sympodialis, Mala s 1, is present on the cell surface of the yeast. Recombinant Mala s 1 was expressed in Escherichia coli, purified and refolded in a soluble form. Crystals of Mala s 1 were obtained in 25% PEG 8K, 0.2 M (NH{sub 4}){sub 2}SO{sub 4}. Crystals belong to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 44.4, b = 163.7, c = 50.6 Å, and diffract to 1.35 Å resolution.

  9. Creation of a S1P Lyase bacterial surrogate for structure-based drug design.

    PubMed

    Argiriadi, Maria A; Banach, David; Radziejewska, Elzbieta; Marchie, Susan; DiMauro, Jennifer; Dinges, Jurgen; Dominguez, Eric; Hutchins, Charles; Judge, Russell A; Queeney, Kara; Wallace, Grier; Harris, Christopher M

    2016-05-01

    S1P Lyase (SPL) has been described as a drug target in the treatment of autoimmune diseases. It plays an important role in maintaining intracellular levels of S1P thereby affecting T cell egress from lymphoid tissues. Several groups have already published approaches to inhibit S1P Lyase with small molecules, which in turn increase endogenous S1P concentrations resulting in immunosuppression. The use of structural biology has previously aided SPL inhibitor design. Novel construct design is at times necessary to provide a reagent for protein crystallography. Here we present a chimeric bacterial protein scaffold used for protein X-ray structures in the presence of early small molecule inhibitors. Mutations were introduced to the bacterial SPL from Symbiobacterium thermophilum which mimic the human enzyme. As a result, two mutant StSPL crystal structures resolved to 2.8Å and 2.2Å resolutions were solved and provide initial structural hypotheses for an isoxazole chemical series, whose optimization is discussed in the accompanying paper.

  10. Conversion therapy for pancreatic cancer with peritoneal metastases using intravenous and intraperitoneal paclitaxel with S-1

    PubMed Central

    Kitayama, Hiromitsu; Tsuji, Yasushi; Kondo, Tomohiro; Sugiyama, Junko; Hirayama, Michiaki; Yamamoto, Kazuyuki; Kawarada, You; Oyamada, Yumiko; Hirano, Satoshi

    2016-01-01

    Combination chemotherapy consisting of systemic and intraperitoneal agents against peritoneal metastases from several types of cancer has shown promising results. We herein report a case in which combination therapy with intravenous and intraperitoneal paclitaxel with S-1 converted an unresectable pancreatic cancer with peritoneal metastases into a resectable one. The patient was a 65-year old woman with recurrent pancreatitis for 5 months. Endoscopic ultrasonography-guided fine-needle aspiration revealed minute epithelial masses composed of cells with irregular nuclei in the pancreatic body. The patient underwent abdominal surgery, but no excision was performed, as two peritoneal metastases in the bursa omentalis were detected. Combination therapy was initiated, consisting of intravenous and intraperitoneal paclitaxel with S-1 as a single-center clinical trial. The regimen consisted with 2-week administration of S-1 (80 mg per day) followed by 1 week of rest, intravenous paclitaxel 50 mg/m2, and intraperitoneal paclitaxel 20 mg/m2 by a peritoneal access device on days 1 and 8. Over the seven cycles of the chemotherapy, the primary lesion did not change in size, and peritoneal lavage cytology remained negative. After confirming the disappearance of the peritoneal lesions by exploratory laparoscopy, the patient underwent distal pancreatectomy combined with resection of the transverse mesocolon and stomach wall. Thus, the 2-way chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 was well-tolerated and was able to convert pancreatic cancer with peritoneal metastases to resectable disease. PMID:28105356

  11. Fundamental linewidth in solitary, ultranarrow output PbS(1-x)Se(x) diode lasers

    NASA Technical Reports Server (NTRS)

    Freed, C.; Bielinski, J. W.; Lo, W.

    1983-01-01

    The fundamental, quantum phase noise limited Lorentzian linewidth was directly measured from the beat-note spectra generated by heterodyning PbS(1-x)Se(x) diode lasers with a stable CO gas laser. The experimental results were matched by calculated theoretical line profiles. Linewidths as narrow as 22 kHz full width at half-maximum power were observed.

  12. Robustness of S1 statistic with Hodges-Lehmann for skewed distributions

    NASA Astrophysics Data System (ADS)

    Ahad, Nor Aishah; Yahaya, Sharipah Soaad Syed; Yin, Lee Ping

    2016-10-01

    Analysis of variance (ANOVA) is a common use parametric method to test the differences in means for more than two groups when the populations are normally distributed. ANOVA is highly inefficient under the influence of non- normal and heteroscedastic settings. When the assumptions are violated, researchers are looking for alternative such as Kruskal-Wallis under nonparametric or robust method. This study focused on flexible method, S1 statistic for comparing groups using median as the location estimator. S1 statistic was modified by substituting the median with Hodges-Lehmann and the default scale estimator with the variance of Hodges-Lehmann and MADn to produce two different test statistics for comparing groups. Bootstrap method was used for testing the hypotheses since the sampling distributions of these modified S1 statistics are unknown. The performance of the proposed statistic in terms of Type I error was measured and compared against the original S1 statistic, ANOVA and Kruskal-Wallis. The propose procedures show improvement compared to the original statistic especially under extremely skewed distribution.

  13. Bioremediation of wastewater from edible oil refinery factory using oleaginous microalga Desmodesmus sp. S1.

    PubMed

    Mar, Cho Cho; Fan, Yong; Li, Fu-Li; Hu, Guang-Rong

    2016-12-01

    Edible oil industry produced massive wastewater, which requires extensive treatment to remove pungent smell, high phosphate, carbon oxygen demand (COD), and metal ions prior to discharge. Traditional anaerobic and aerobic digestion could mainly reduce COD of the wastewater from oil refinery factories (WEORF). In this study, a robust oleaginous microalga Desmodesmus sp. S1 was adapted to grow in WEORF. The biomass and lipid content of Desmodesmus sp. S1 cultivated in the WEORF supplemented with sodium nitrate were 5.62 g·L(-1) and 14.49%, whereas those in the WEORF without adding nitrate were 2.98 g·L(-1) and 21.95%. More than 82% of the COD and 53% of total phosphorous were removed by Desmodesmus sp. S1. In addition, metal ions, including ferric, aluminum, manganese and zinc were also diminished significantly in the WEORF after microalgal growth, and pungent smell vanished as well. In comparison with the cells grown in BG-11 medium, the cilia-like bulges and wrinkles on the cell surface of Desmodesmus sp. S1 grown in WEORF became out of order, and more polyunsaturated fatty acids were detected due to stress derived from the wastewater. The study suggests that growing microalgae in WEORF can be applied for the dual roles of nutrient removal and biofuel feedstock production.

  14. High-Dispersion Spectroscopic Observations of Comet C/2012 S1 (ISON) with the Subaru Telescope

    NASA Astrophysics Data System (ADS)

    Shinnaka, Yoshiharu; Kawakita, Hideyo; Nagashima, Masayoshi; Hitomi, Kobayashi; Decock, Alice; Jehin, Emmanuel; Boice, Daniel C.

    2014-11-01

    Comet C/2012 S1 (ISON) was one of the Oort cloud comets and dynamically new. This comet was broken at its perihelion passage on UT 2013 November 28.1 (at Rh ~ 17 solar radius). We observed the comet C/2012 S1 (ISON) on UT 2013 November 15 with the High Dispersion Spectrograph (HDS) mounted on the Subaru Telescope atop Mauna Kea, Hawaii. Its heliocentric and geocentric distances were 0.601 and 0.898 AU, respectively. We selected the slit size of 0”.5 x 9”.0 on the sky to achieve the spectral resolution of R = 72,000 from 550 to 830 nm. The total exposure time of comet C/2012 S1 (ISON) was 1200 seconds. We detected many emission lines caused from radicals (e.g., CN, C2, NH2), ions (H2O+), atoms ([OI] and Na I) and also many unidentified lines in the spectra. We report the (1) the ortho-to-para abundance ratios (OPRs) of water and ammonia estimated from the high-dispersion spectra of H2O+ and NH2, (2) the green-to-red line ratio of forbidden oxygen emissions, (3) the isotopic ratios of C2 (the carbon isotopic ratio from Swan band) and CN (the carbon and nitrogen isotopic ratios from red band), (4) the sodium-to-continuum ratio of comet C/2012 S1 (ISON).

  15. Determination of the hyperfine coupling constant of the cesium 7S1/2 state

    NASA Astrophysics Data System (ADS)

    Yang, Guang; Wang, Jie; Yang, Baodong; Wang, Junmin

    2016-08-01

    We report the hyperfine splitting (HFS) measurement of the cesium (Cs) 7S1/2 state by optical-optical double-resonance spectroscopy with the Cs 6S1/2-6P3/2-7S1/2 (852 nm  +  1470 nm) ladder-type system. The HFS frequency calibration is performed by employing a phase-type waveguide electro-optic modulator together with a stable confocal Fabry-Perot cavity. From the measured HFS between the F″  =  3 and F″  =  4 manifolds of the Cs 7S1/2 state (HFS  =  2183.273  ±  0.062 MHz), we have determined the magnetic dipole hyperfine coupling constant (A  =  545.818  ±  0.016 MHz), which is in good agreement with the previous work but much more precise.

  16. Universality of the Ising and the S=1 model on Archimedean lattices: A Monte Carlo determination

    NASA Astrophysics Data System (ADS)

    Malakis, A.; Gulpinar, G.; Karaaslan, Y.; Papakonstantinou, T.; Aslan, G.

    2012-03-01

    The Ising models S=1/2 and S=1 are studied by efficient Monte Carlo schemes on the (3,4,6,4) and the (3,3,3,3,6) Archimedean lattices. The algorithms used, a hybrid Metropolis-Wolff algorithm and a parallel tempering protocol, are briefly described and compared with the simple Metropolis algorithm. Accurate Monte Carlo data are produced at the exact critical temperatures of the Ising model for these lattices. Their finite-size analysis provide, with high accuracy, all critical exponents which, as expected, are the same with the well-known 2D Ising model exact values. A detailed finite-size scaling analysis of our Monte Carlo data for the S=1 model on the same lattices provides very clear evidence that this model obeys, also very well, the 2D Ising model critical exponents. As a result, we find that recent Monte Carlo simulations and attempts to define effective dimensionality for the S=1 model on these lattices are misleading. Accurate estimates are obtained for the critical amplitudes of the logarithmic expansions of the specific heat for both models on the two Archimedean lattices.

  17. 75 FR 7027 - Airworthiness Directives; Turbomeca Arriel 2S1 Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-16

    ... applies to Turbomeca Arriel 2S1 turboshaft engines that have not incorporated Modification TU 109. These...) software to version 11.01, to implement modification TU 109. (2) Guidance on implementing TU 109 can be... twin-engine helicopter with one engine upgraded to modification TU 109 if the other engine is...

  18. Pan-STARRS 1 observations of the unusual active Centaur P/2011 S1(Gibbs)

    SciTech Connect

    Lin, H. W.; Ip, W. H.; Chen, W. P.; Chen, Y. T.; Lacerda, P.; Holman, M.; Protopapas, P.; Burgett, W. S.; Chambers, K. C.; Flewelling, H.; Huber, M. E.; Jedicke, R.; Kaiser, N.; Magnier, E. A.; Metcalfe, N.; Price, P. A.

    2014-05-01

    P/2011 S1 (Gibbs) is an outer solar system comet or active Centaur with a similar orbit to that of the famous 29P/Schwassmann-Wachmann 1. P/2011 S1 (Gibbs) has been observed by the Pan-STARRS 1 (PS1) sky survey from 2010 to 2012. The resulting data allow us to perform multi-color studies of the nucleus and coma of the comet. Analysis of PS1 images reveals that P/2011 S1 (Gibbs) has a small nucleus <4 km radius, with colors g {sub P1} – r {sub P1} = 0.5 ± 0.02, r {sub P1} – i {sub P1} = 0.12 ± 0.02, and i {sub P1} – z {sub P1} = 0.46 ± 0.03. The comet remained active from 2010 to 2012, with a model-dependent mass-loss rate of ∼100 kg s{sup –1}. The mass-loss rate per unit surface area of P/2011 S1 (Gibbs) is as high as that of 29P/Schwassmann-Wachmann 1, making it one of the most active Centaurs. The mass-loss rate also varies with time from ∼40 kg s{sup –1} to 150 kg s{sup –1}. Due to its rather circular orbit, we propose that P/2011 S1 (Gibbs) has 29P/Schwassmann-Wachmann 1-like outbursts that control the outgassing rate. The results indicate that it may have a similar surface composition to that of 29P/Schwassmann-Wachmann 1. Our numerical simulations show that the future orbital evolution of P/2011 S1 (Gibbs) is more similar to that of the main population of Centaurs than to that of 29P/Schwassmann-Wachmann 1. The results also demonstrate that P/2011 S1 (Gibbs) is dynamically unstable and can only remain near its current orbit for roughly a thousand years.

  19. The S1 Truss Prior to Installation on the International Space Station

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Being attached to the Canadarm2 on the International Space Station (ISS), the Remote Manipulator System arm built by the Canadian Space Agency, the Integrated Truss Assembly (S1) Truss is suspended over the Space Shuttle Orbiter Atlantis' cargo bay. Astronauts Sandra H. Magnus, STS-112 mission specialist, and Peggy A. Whitson, Expedition Five flight engineer, used the Canadarm2 from inside the Destiny laboratory on the ISS to lift the S1 truss out of the orbiter's cargo bay and move it into position prior to its installation on the ISS. The primary payloads of this mission, ISS Assembly Mission 9A, were the Integrated Truss Assembly S1 (S One), the starboard side thermal radiator truss, and the Crew Equipment Translation Aid (CETA) cart to the ISS. The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss was attached to the S0 (S Zero) truss, which was launched on April 8, 2002 aboard the STS-110, and flows 637 pounds of anhydrous ammonia through three heat-rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA cart was attached to the Mobil Transporter and will be used by assembly crews on later missions. Manufactured by the Boeing Company in Huntington Beach, California, the truss primary structure was transferred to the Marshall Space Flight Center in February 1999 for hardware installations and manufacturing acceptance testing. The launch of the STS-112 mission occurred on October 7, 2002, and its 11-day mission ended on October 18, 2002.

  20. Centennial-scale paleoceanography during sapropel S1 deposition in the NE Aegean (Mediterranean Sea)

    NASA Astrophysics Data System (ADS)

    Triantaphyllou, Maria; Gogou, Alexandra; Dimiza, Margarita; Kostopoulou, Sofia; Parinos, Constantine; Roussakis, Grigoris; Geraga, Maria; Skampa, Elisavet; Bouloubassi, Ioanna; Fleitmann, Dominik; Zervakis, Vassilis; Velaoras, Dimitris; Diamantopoulou, Antonia; Sampatakaki, Angeliki; Lykousis, Vassilis

    2016-04-01

    Combined micropaleontological and geochemical analyses in the high-sedimentation gravity core M-4G, provided new centennial scale paleoceanographic data for the sapropel S1 deposition in the NE Aegean Sea. Sapropel layer S1a (10.2-8.0 ka) is deposited in dysoxic to oxic bottom waters; sediments are characterized by the high abundance of benthic foraminifers Chilostomella mediterranensis and Globobulimina affinis that are able to tolerate surface sediment and/or pore water oxygen depletion and the presence of the oxic mesotrophic-eutrophic U. mediterranea. Adequate preservation of organic matter is proven by the high organic carbon and loliolide and isololiolide contents, whereas the biomarker record and the abundances of eutrophic planktonic foraminifera document enhanced productivity. Both alkenone-based SSTs and δO18 G. bulloides records indicate coolings at 8.2 ka (S1a) and at ~7.8 ka (S1 interruption). Sapropelic layer S1b (7.7-6.4 ka) is characterized by rather oxic conditions marked by the prominent increase of U. mediterranea. The highly fluctuating SSTs demonstrate repeated coolings and associated dense water formation; major event at 7.4 ka, followed by cold spells at 7.0, 6.8, 6.5 ka. Besides, the increase of algal biomarkers, labile organic matter-feeding foraminifera and eutrophic planktonic species pinpoints rise in in situ marine productivity, which is enhanced by more efficient vertical convection due to repeated cold events. The associated contributions of labile marine organic matter (OM) along with fresher terrestrial OM inputs after ~7.7 ka BP imply alternative/ additional than the north Aegean riverine borderland sources for the influx of organic matter at the south Limnos Basin, also related to the inflow of highly productive Marmara/Black Sea waters

  1. Index theorem for topological excitations on R3 × S1 and Chern-Simons theory

    NASA Astrophysics Data System (ADS)

    Poppitz, Erich; Ünsal, Mithat

    2009-03-01

    We derive an index theorem for the Dirac operator in the background of various topological excitations on an R3 × S1 geometry. The index theorem provides more refined data than the APS index for an instanton on R4 and reproduces it in decompactification limit. In the R3 limit, it reduces to the Callias index theorem. The index is expressed in terms of topological charge and the η-invariant associated with the boundary Dirac operator. Neither topological charge nor η-invariant is typically an integer, however, the non-integer parts cancel to give an integer-valued index. Our derivation is based on axial current non-conservation — an exact operator identity valid on any four-manifold — and on the existence of a center symmetric, or approximately center symmetric, boundary holonomy (Wilson line). We expect the index theorem to usefully apply to many physical systems of interest, such as low temperature (large S1, confined) phases of gauge theories, center stabilized Yang-Mills theories with vector-like or chiral matter (at S1 of any size), and supersymmetric gauge theories with supersymmetry-preserving boundary conditions (also at any S1). In QCD-like and chiral gauge theories, the index theorem should shed light into the nature of topological excitations responsible for chiral symmetry breaking and the generation of mass gap in the gauge sector. We also show that imposing chirally-twisted boundary condition in gauge theories with fermions induces a Chern-Simons term in the infrared. This suggests that some QCD-like gauge theories should possess components with a topological Chern-Simons phase in the small S1 regime.

  2. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme.

    PubMed

    Bien-Möller, Sandra; Lange, Sandra; Holm, Tobias; Böhm, Andreas; Paland, Heiko; Küpper, Johannes; Herzog, Susann; Weitmann, Kerstin; Havemann, Christoph; Vogelgesang, Silke; Marx, Sascha; Hoffmann, Wolfgang; Schroeder, Henry W S; Rauch, Bernhard H

    2016-03-15

    A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient´s survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient´s survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells.In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation.

  3. Investigating the molecular mechanisms through which FTY720-P causes persistent S1P1 receptor internalization

    PubMed Central

    Sykes, David A; Riddy, Darren M; Stamp, Craig; Bradley, Michelle E; McGuiness, Neil; Sattikar, Afrah; Guerini, Danilo; Rodrigues, Ines; Glaenzel, Albrecht; Dowling, Mark R; Mullershausen, Florian; Charlton, Steven J

    2014-01-01

    Background and Purpose The molecular mechanism underlying the clinical efficacy of FTY720-P is thought to involve persistent internalization and enhanced degradation of the S1P1 receptor subtype (S1P1R). We have investigated whether receptor binding kinetics and β-arrestin recruitment could play a role in the persistent internalization of the S1P1R by FTY720-P. Experimental Approach [3H]-FTY720-P and [33P]-S1P were used to label CHO-S1P1/3Rs for binding studies. Ligand efficacy was assessed through [35S]-GTPγS binding and β-arrestin recruitment. Metabolic stability was evaluated using a bioassay measuring intracellular Ca2+ release. CHO-S1P1/3R numbers were determined, following FTY720-P treatment using flow cytometry. Key Results The kinetic off-rate of [3H]-FTY720-P from the S1P1R was sixfold slower than from the S1P3R, and comparable to [33P]-S1P dissociation from S1P1/3Rs. S1P and FTY720-P stimulated [35S]-GTPγS incorporation to similar degrees, but FTY720-P was over 30-fold less potent at S1P3Rs. FTY720-P stimulated a higher level of β-arrestin recruitment at S1P1Rs, 132% of the total recruited by S1P. In contrast, FTY720-P was a weak partial agonist at S1P3R, stimulating just 29% of the total β-arrestin recruited by S1P. Internalization experiments confirmed that cell surface expression of the S1P1R but not the S1P3R was reduced following a pulse exposure to FTY720-P, which is metabolically stable unlike S1P. Conclusions and Implications FTY720-P and S1P activation of the S1P1R results in receptor internalization as a consequence of an efficient recruitment of β-arrestin. The combination of slow off-rate, efficacious β-arrestin recruitment and metabolic stability all contribute to FTY720-P's ability to promote prolonged S1P1R internalization and may be critical factors in its efficacy in the clinic. PMID:24641481

  4. 40 CFR Table S-1 to Subpart S of... - Basic Parameters for the Calculation of Emission Factors for Lime Production

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Basic Parameters for the Calculation of Emission Factors for Lime Production S Table S-1 to Subpart S of Part 98 Protection of Environment... Manufacturing Pt. 98, Subpt. S, Table S-1 Table S-1 to Subpart S of Part 98—Basic Parameters for the...

  5. The Character of the Long-Lived State Formed from S_1 of Phenylacetylene

    NASA Astrophysics Data System (ADS)

    Johnson, Philip M.; Sears, Trevor J.

    2013-06-01

    Compared to other small aromatic molecules, phenylacetylene (PA) and benzonitrile exhibit strikingly anomalous photophysics on excitation to the S_1 state. Firstly, products are formed on S_1 excitation of a beam-cooled sample that seem to live indefinitely (as defined by the flight time through the apparatus), while action spectra of their formation mirror the rotationally-resolved absorption spectrum of the monomer. Secondly, the long lived products appear immediately during the nsec. laser pulse rather than build up during the lifetime of the singlet level, as is seen in benzene, for example. The question has therefore arisen: is the long lived product of the S_1 excitation the triplet state, as is assumed in all previous work on other molecules, or is it an isomer of some sort? New pump-probe ionization mass spectroscopy experiments have been performed to study the distribution of fragments and metastable ions produced by PA cation derived from the neutral S_1 state, and from the long-lived species. These combined with other experimental results showing weak long-lived components in both the S_1 fluorescence and pump-probe photoelectron spectra that we interpret as recurrence behavior, definitively show the long-lived state is a triplet state of PA, not an isomer. PA with a singlet-triplet gap of 10000 cm^{-1} is acting like intermediate case molecules with much smaller singlet-triplet gaps such as pyrazine and pyrimidine. Calculations point to the existence of four triplet states of PA at or below the energy of S_1 providing a very large density of vibronic states in which to distribute the energy from singlet-triplet crossing. PA T_1 is calculated to be non-planar, in contrast to what is found in benzene, possibly helping to explain the different photophysics. Acknowledgments: We gratefully acknowledge G. V. Lopez for his contributions to some of the experimental masurements. Work at Brookhaven National Laboratory was carried out under Contract No. DE-AC02

  6. [Side effects analyses in consideration of renal function for S-1-administered patients].

    PubMed

    Iwai, Mina; Kimura, Michio; Yoshimura, Tomoaki; Yasuda, Tadashi

    2011-06-01

    Although many analyses of S-1 side effects are reported, there are no reports where the analyses of side effects were performed in consideration of renal function, which is an important index of medication dose. Therefore, we investigated side effects in consideration of renal function. The subjects were 163 patients administered S-1 at the Department of Surgery of Ogaki Municipal Hospital, between October 2008 and December 2009. The frequency and severity of side effects were high and serious in the groupwhose creatinine clearance was low. A significant difference was observed among 3 groups with regard to thrombocytopenia and dehydration. In conclusion, we think that pharmacists must take renal function into consideration when administering medication, to keepclose medicinal guidance, and to actively observe progress.

  7. Raman spectrum of bacteriochlorophyll a in the S1 state

    NASA Astrophysics Data System (ADS)

    Nishizawa, Ei-ichi; Hashimoto, Hideki; Koyama, Yasushi

    1991-07-01

    The S 1 Raman spectrum of bacteriochlorophyll a is reported for the first time. A one-color experiment using the 351 nm picosecond pulses (duration 50 ps and repetition 1 kHz) for tetrahydrofuran solution detected a transient species, which showed distinct Raman lines at 1567, 1409 and 1320 cm -1 and weak profiles around 1169, 1092, 1051 and 794 cm -1. The other one-color experiment using the 355 nm nanosecond pulses (duration 12 ns and repetition 10 Hz) detected the T 1 species reported previously showing Raman lines at 1578 and 1330 cm -1. Thus, the newly identified transient species, which was pumped and probed within 50 ps, is assigned to S 1.

  8. Physical Contact between the +20 km s-1 Cloud and the Galactic Circumnuclear Disk

    NASA Astrophysics Data System (ADS)

    Takekawa, Shunya; Oka, Tomoharu; Tanaka, Kunihiko

    2017-01-01

    We report the discovery of physical contact between the Galactic circumnuclear disk (CND) and an adjacent giant molecular cloud. The central 10 pc of our Galaxy has been imaged in molecular lines at millimeter wavelength using the Nobeyama Radio Observatory 45 m radio telescope. In the position-velocity maps of several high-density probe lines, we have found an emission ``bridge'' connecting the +20 km s-1 cloud (M-0.13-0.08) and the negative longitude extension of the CND. The collision between the +20 km s-1 cloud and the CND may be responsible for the formation of the bridge. This event can promote mass accretion onto the CND and/or into the inner cavity.

  9. Structural deformation of the S =1 kagome-lattice compound KV3Ge2O9

    NASA Astrophysics Data System (ADS)

    Takagi, Eigo; Aoyama, Takuya; Hara, Shigeo; Sato, Hirohiko; Kimura, Tsuyoshi; Wakabayashi, Yusuke

    2017-03-01

    The dielectric and structural properties of the S =1 kagome antiferromagnet KV3Ge2O9 are examined. The low-temperature structure below 50 K is orthorhombic with a typical correlation length of 8 nm. While the high-temperature hexagonal phase can be considered C -centered orthorhombic, the C -centered symmetry is broken below 50 K. The low-temperature symmetry does not support the simplex solid state, which is the theoretically expected ground state for the S =1 kagome lattice. Above 60 K, incommensurate lattice modulation is observed. The lock-in transition suggests that the origin of the orthorhombic deformation is the development of a short-range magnetic ordering.

  10. Mapping of Epitopes Occurring in Bovine α(s1)-Casein Variants by Peptide Microarray Immunoassay.

    PubMed

    Lisson, Maria; Erhardt, Georg

    2016-01-01

    Immunoglobulin E epitope mapping of milk proteins reveals important information about their immunologic properties. Genetic variants of αS1-casein, one of the major allergens in bovine milk, are until now not considered when discussing the allergenic potential. Here we describe the complete procedure to assess the allergenicity of αS1-casein variants B and C, which are frequent in most breeds, starting from milk with identification and purification of casein variants by isoelectric focusing (IEF) and anion-exchange chromatography, followed by in vitro gastrointestinal digestion of the casein variants, identification of the resulting peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), in silico analysis of the variant-specific peptides as allergenic epitopes, and determination of their IgE-binding properties by microarray immunoassay with cow's milk allergic human sera.

  11. Superconformal index on R P2×S1 and mirror symmetry

    NASA Astrophysics Data System (ADS)

    Tanaka, Akinori; Mori, Hironori; Morita, Takeshi

    2015-05-01

    We study N =2 supersymmetric gauge theories on RP 2×S1 and compute the superconformal index by using the localization technique. We consider not only the round real projective plane RP 2 but also the squashed real projective plane RPb 2 which turns back to RP 2 by taking a squashing parameter b as 1. In addition, we find that the result is independent of the squashing parameter b . We apply our new superconformal index to check the simplest case of 3D mirror symmetry, i.e., the equivalence between the N =2 supersymmetric quantum electrodynamics (SQED) and the X Y Z model on RP 2×S1. We prove it by using a mathematical formula called the q -binomial theorem. We also comment on the N =4 version of mirror symmetry, mirror symmetry via generalized indices, and possibilities of generalizations from mathematical viewpoints.

  12. Ising Model Spin S = 1 ON Directed BARABÁSI-ALBERT Networks

    NASA Astrophysics Data System (ADS)

    Lima, F. W. S.

    On directed Barabási-Albert networks with two and seven neighbours selected by each added site, the Ising model with spin S = 1/2 was seen not to show a spontaneous magnetisation. Instead, the decay time for flipping of the magnetisation followed an Arrhenius law for Metropolis and Glauber algorithms, but for Wolff cluster flipping the magnetisation decayed exponentially with time. On these networks the Ising model spin S = 1 is now studied through Monte Carlo simulations. However, in this model, the order-disorder phase transition is well defined in this system. We have obtained a first-order phase transition for values of connectivity m = 2 and m = 7 of the directed Barabási-Albert network.

  13. Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice.

    PubMed

    Rieck, Michael; Kremser, Christiane; Jobin, Katarzyna; Mettke, Elisabeth; Kurts, Christian; Gräler, Markus; Willecke, Klaus; Kolanus, Waldemar

    2017-02-15

    Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine. We, therefore, investigated whether Cers2 is involved in the regulation of S1P gradients and S1P-dependent egress into the circulation. By analyzing Cers2-deficient mice, we demonstrate that Cers2 limits the levels of S1P in thymus and blood to maintain functional S1P gradients that mediate thymocyte emigration into the circulation. This function is specific for Cers2, as we also show that Cers4 is not involved in the regulation of thymic egress. Our study identified Cers2 as an important regulator of S1P-dependent thymic egress, and thus contributes to the understanding of how S1P gradients are maintained in vivo.

  14. Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival.

    PubMed

    Jaillard, C; Harrison, S; Stankoff, B; Aigrot, M S; Calver, A R; Duddy, G; Walsh, F S; Pangalos, M N; Arimura, N; Kaibuchi, K; Zalc, B; Lubetzki, C

    2005-02-09

    Endothelial differentiation gene (Edg) proteins are G-protein-coupled receptors activated by lysophospholipid mediators: sphingosine-1-phosphate (S1P) or lysophosphatidic acid. We show that in the CNS, expression of Edg8/S1P5, a high-affinity S1P receptor, is restricted to oligodendrocytes and expressed throughout development from the immature stages to the mature myelin-forming cell. S1P activation of Edg8/S1P5 on O4-positive pre-oligodendrocytes induced process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway, whereas no retraction was elicited by S1P on these cells derived from Edg8/S1P5-deficient mice. Edg8/S1P5-mediated process retraction was restricted to immature cells and was no longer observed at later developmental stages. In contrast, S1P activation promoted the survival of mature oligodendrocytes but not of pre-oligodendrocytes. The S1P-induced survival of mature oligodendrocytes was mediated through a pertussis toxin-sensitive, Akt-dependent pathway. Our data demonstrate that Edg8/S1P5 activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival and that these effects depend on the developmental stage of the cell.

  15. Complete Measurement of S(1D2) Photofragment Alignment from Abel-Invertible Ion Images

    NASA Astrophysics Data System (ADS)

    Rakitzis, T. Peter; Samartzis, Peter C.; Kitsopoulos, Theofanis N.

    2001-09-01

    A novel method to measure directly the photofragment alignment from Abel-invertible two-dimensional ion images, as a function of photofragment recoil velocity, is demonstrated for S(1D2) atoms from the photodissociation of carbonyl sulfide at 223 nm. The results are analyzed in terms of coherent and incoherent contributions from two dissociative states, showing that the phase differences of the asymptotic wave functions of the fast and slow recoil-velocity channel are approximately π/2 and 0, respectively.

  16. Room for an S=+1 pentaquark in K+-nucleus phenomenology

    NASA Astrophysics Data System (ADS)

    Gal, A.; Friedman, E.

    2006-01-01

    Evidence for excitation of exotic S=+1 pentaquark degrees of freedom is presented by studying optical-potential fits to K+-nucleus total, reaction and elastic-differential cross section data at plab~500-700 MeV/c. Estimates of the underlying two-nucleon absorption K+nN→Θ+N reaction cross section are made and are used for discussing the anticipated cross section of the strangeness exchange reaction K+N→πΘ+.

  17. Regarding the Charmed-Strange Member of the 23S1 Meson State

    PubMed Central

    Feng, Xue-Chao; Chen, Jing

    2013-01-01

    By employing the mass relations derived from the mass matrix and Regge trajectory, we investigate the masses of charmed and charmed-strange members of the 23S1 meson. The masses are compared with the values predicted by other theoretical approaches and experimental data. The results may be useful for the discovery of the unobserved meson and the determination of the quantum number of the newly discovered states. PMID:24250272

  18. Electroluminescence spectra of rare-earth-doped ZnS 1-XSe X thin films

    NASA Astrophysics Data System (ADS)

    Miura, Noboru; Ogawa, Kiyoshi; Kobayashi, Shuko; Matsumoto, Hironaga; Nakano, Ryotaro

    1994-04-01

    Electroluminescence has been measured for ZnS 1- XSe X thin films doped with rare-earth ions. As X increases the band-gap energy of the host decreases. The emission levels of trivalent rare-earth ions are not observed when the band-gap energy is narrower than the excitation levels. This is because of the energy transfer between the host and the emission center.

  19. Application of the S=1 underscreened Anderson lattice model to Kondo uranium and neptunium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing the coexistence of the Kondo screening effect and ferromagnetic order are investigated within the Anderson lattice Hamiltonian with a two-fold degenerate f level in each site, corresponding to 5f2 electronic configuration with S=1 spins. A derivation of the Schrieffer-Wolff transformation is presented and the resulting Hamiltonian has an effective f-band term, in addition to the regular exchange Kondo interaction between the S=1 f spins and the s=1/2 spins of the conduction electrons. The resulting effective Kondo lattice model can describe both the Kondo regime and a weak delocalization of the 5f electrons. Within this model we compute the Kondo and Curie temperatures as a function of model parameters, namely the Kondo exchange interaction constant JK, the magnetic intersite exchange interaction JH, and the effective f bandwidth. We deduce, therefore, a phase diagram of the model which yields the coexistence of the Kondo effect and ferromagnetic ordering and also accounts for the pressure dependence of the Curie temperature of uranium compounds such as UTe.

  20. Synchronous Basin-Wide Formation and Redox-Controled Preservation of Mediterranean s1 Sapropel

    NASA Astrophysics Data System (ADS)

    De Lange, G. J.; Slomp, C. P.; Corselli, C.; Erba, E.; Thomson, J.; Reitz, A.

    2012-12-01

    Deposition of distinct organic-rich units (sapropels) in eastern Mediterraneran sediments is precession-related and associated with humid climate conditions. The last of such 'humid periods' occurred from 11 - 5 kyr 14C ago, simultaneous with a sustained circum-Mediterranean wet period. The end of this period coincides with a high manganeseoxide peak in all 30 studied cores and concurs with an abrupt re-ventilation event at 5.7 kyr. We demonstrate that the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1 formation (De Lange ea., 2008). This has resulted in a differential basin-wide preservation of S1 determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. Climate-induced stratification of the ocean may thus contribute to enhanced preservation of organic matter, ie formation of sapropels (and potentially black shales)

  1. S-1 monotherapy in a patient with cholangiolocellular carcinoma: A case report

    PubMed Central

    Yamaguchi, Takashi; Seki, Toshihito; Inokuchi, Ryosuke; Kawamura, Rinako; Murata, Miki; Matsuzaki, Koichi; Nakashima, Osamu; Kumabe, Tsutomu; Okazaki, Kazuichi

    2016-01-01

    A 71-year-old man with alcoholic cirrhosis was found to have multiple hypervascular lesions in the liver on enhanced computed tomography. An ultrasound-guided biopsy of the lesion was performed. Immunohistochemical analysis for hepatocyte paraffin 1 expression was negative; cytokeratin (CK) 7, CK19, epithelial cell adhesion molecule and epithelial membrane antigens were positive; mucicarmine staining was negative. The tumor was thus histologically diagnosed as cholangiolocellular carcinoma (CoCC). The tumor was inoperable due to the associated advanced liver disease. In addition, the patient preferred systemic chemotherapy using only orally administered agents. Thus, S-1 monotherapy was recommended. S-1 was initially administered orally at a dose of 80 mg/day. Although the levels of tumor marker (prothrombin induced by vitamin K absence/antagonist-II and carbohydrate antigen 19-9) levels were marginally elevated, their values did not change over the entire course. The patient achieved a partial response according to the Response Evaluation Criteria In Solid Tumors (RECIST) and modified RECIST 1 year after chemotherapy initiation. In conclusion, S-1 monotherapy exhibited promising efficacy against unresectable CoCC. PMID:28105354

  2. Alternative nonallelic deletion is constitutive of ruminant alpha(s1)-casein.

    PubMed

    Ferranti, P; Lilla, S; Chianese, L; Addeo, F

    1999-07-01

    Multiple forms of alpha(s1)-casein were identified in the four major ruminant species by structural characterization of the protein fraction. While alpha(s1)-casein phenotypes were constituted by a mixture of at least seven molecular forms in ovine and caprine species, there were only two forms in bovine and water buffalo species. In ovine and caprine forms the main component corresponded to the 199-residue-long form, and the deleted proteins differed from the complete one by the absence of peptides 141-148, 110-117, or Gln78, or a combination of such deletions. The deleted segments corresponded to the sequence regions encoded by exons 13 and 16, and by the first triplet of exon 11 (CAG), suggesting that the occurrence of the short protein forms is due to alternative skipping, as previously demonstrated for some caprine and ovine phenotypes. The alternative deletion of Gln78 in alpha(s1)-casein, the only form common to the milk of all the species examined and located in a sequence region joining the polar phosphorylation cluster and the hydrophobic C-terminal domain of the protein, may play a functional role in the stabilization of the milk micelle structure.

  3. On the Absence of EUV Emission from Comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Bryans, Paul; Pesnell, W. Dean

    2016-05-01

    When the sungrazing comet C/2012 S1 (ISON) made its perihelion passage within two solar radii of the Sun’s surface, it was expected to be a bright emitter at extreme ultraviolet (EUV) wavelengths. However, despite solar EUV telescopes repointing to track the orbit of the comet, no emission was detected. This “null result” is interesting in its own right, offering the possibility of placing limits on the size and composition of the nucleus. We explain the lack of detection by considering the properties of the comet and the solar atmosphere that determine the intensity of EUV emission from sungrazing comets. By comparing these properties with those of sungrazing comet C/2011 W3 (Lovejoy), which did emit in the EUV, we conclude that the primary factor resulting in non-detectable EUV emission from C/2012 S1 (ISON) was an insufficiently large nucleus. We conclude that the radius of C/2012 S1 (ISON) was at least a factor of four less than that of C/2011 W3 (Lovejoy). This is consistent with white-light observations in the days before perihelion that suggested the comet was dramatically reducing in size on approach.

  4. Short Time-Scale Sensory Coding in S1 during Discrimination of Whisker Vibrotactile Sequences

    PubMed Central

    Miyashita, Toshio; Lee, Daniel J.; Smith, Katherine A.; Feldman, Daniel E.

    2016-01-01

    Rodent whisker input consists of dense microvibration sequences that are often temporally integrated for perceptual discrimination. Whether primary somatosensory cortex (S1) participates in temporal integration is unknown. We trained rats to discriminate whisker impulse sequences that varied in single-impulse kinematics (5–20-ms time scale) and mean speed (150-ms time scale). Rats appeared to use the integrated feature, mean speed, to guide discrimination in this task, consistent with similar prior studies. Despite this, 52% of S1 units, including 73% of units in L4 and L2/3, encoded sequences at fast time scales (≤20 ms, mostly 5–10 ms), accurately reflecting single impulse kinematics. 17% of units, mostly in L5, showed weaker impulse responses and a slow firing rate increase during sequences. However, these units did not effectively integrate whisker impulses, but instead combined weak impulse responses with a distinct, slow signal correlated to behavioral choice. A neural decoder could identify sequences from fast unit spike trains and behavioral choice from slow units. Thus, S1 encoded fast time scale whisker input without substantial temporal integration across whisker impulses. PMID:27574970

  5. Identification of New {CIS} Vibrational Levels in the S1 State of C2H2

    NASA Astrophysics Data System (ADS)

    Baraban, J. H.; Changala, P. B.; Shaver, R. G.; Field, R. W.; Stanton, J. F.; Merer, A. J.

    2012-06-01

    Although the S_1 (tilde{A} ^1A_u) state of the trans conformer of acetylene has been known for many years, the corresponding S_1 (tilde{A} ^1A_2) state of the cis conformer was only discovered recently. Transitions to it from the ground state are electronically forbidden, but its vibrational levels acquire intensity by tunneling through the isomerization barrier and interacting with levels of the trans conformer. We have recently identified two new vibrational levels (32 and 41 61) of the {cis} conformer of S1 C2H2, bringing the total number of levels observed to six out of an expected ten up to the energies studied in this work. The appearance of these levels in IR-UV double resonance LIF spectra will be discussed, along with their vibrational assignments. Experimentally determined vibrational parameters and {ab initio} anharmonic force fields for both the {trans} and {cis} conformers will be presented as part of the evidence supporting these assignments. These results shed new light on the vibrational level structure of both conformers in this isomerizing system. A. J. Merer, A. H. Steeves, J. H. Baraban, H. A. Bechtel, and R. W. Field. J. Chem. Phys., 134(24):244310, 2011.

  6. Hyperconjugation in the S1 State of Substituted Toluene Probed by Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Chiba, Takashi; Okuyama, Katsuhiko; Fujii, Asuka

    2016-06-01

    Internal rotation of the methyl group in substituted toluenes is one of prototypes of large amplitude motions in polyatomic molecules. The internal rotation of o-fluorotoluene is strongly hindered in the S0 state, but that of m-fluorotoluene is almost free. For the S1 state, however, the substantial changes of the internal rotation potentials have been reported; while the potential barrier in the o-isomer drastically decreases and the methyl group becomes almost a free rotor, the barrier in the m-isomer largely increases. These surprising barrier changes have been attributed to the methyl conformation-dependent stabilization in the S1 state by the π*-σ* hyperconjugation. In the present study, to test this interpretation, we observed infrared spectra of o- and m-fluorotoluenes in the S0 and S1 states. Both the isomers showed decrease of the methyl CH stretch frequencies upon the electronic excitation. We concluded that this frequency decrease is the evidence of the π*-σ* hyperconjugation. K,Okuyama.;N,Mikami.;M,Ito. J.Phys.Chem. 1985, 89, 5617 H,Nakai.;M,Kawai. Chem.Phys.Lett 1999, 307, 272

  7. Correlation of charge, hydrophobicity, and structure with antimicrobial activity of S1 and MIRIAM peptides.

    PubMed

    Leptihn, Sebastian; Har, Jia Yi; Wohland, Thorsten; Ding, Jeak Ling

    2010-11-02

    Antimicrobial peptides are key elements of the innate immune system. Many of them interact with membranes of bacteria leading to perturbation of the lipid bilayer and eventually to inactivation of the pathogen. The emergence of multidrug-resistant bacteria has necessitated innovations of new and more powerful classes of antimicrobials. Here we present the in-depth study of an antimicrobial peptide, MIRIAM, derived from Sushi1 (S1), a well-characterized peptide from the horseshoe crab. MIRIAM interacts strongly with negatively charged lipids, forming an α-helical structure. MIRIAM was found to neutralize LPS and kill Gram-negative bacteria with high efficiency, while not releasing LPS. The promising therapeutic potential of MIRIAM is shown by hemolytic assays, which demonstrate that eukaryotic membranes are unaffected at bactericidal concentrations. Nanoparticle-conjugated MIRIAM used in single-molecule fluorescence and electron microscopy experiments showed that MIRIAM targets bacterial membranes to kill bacteria similarly to parental S1. Furthermore, fragments derived from MIRIAM and S1 provided insights on their molecular mechanisms of action, in particular, the relationships of functional motifs comprised by charge, hydrophobicity, and structure within each peptide. We conclude that the combination of charge, hydrophobicity, and length of the peptide is important. A close interaction of amino acids in a single molecule in a carefully balanced ensemble of sequence position and secondary structure is crucial.

  8. Cloning and characterization of a gene from Rhizobium melilotii 2011 coding for ribosomal protein S1.

    PubMed Central

    Schnier, J; Thamm, S; Lurz, R; Hussain, A; Faist, G; Dobrinski, B

    1988-01-01

    A 7 kb chromosomal DNA fragment from R. melilotii was cloned, which complemented temperature-sensitivity of an E. coli amber mutant in rpsA, the gene for ribosomal protein S1 (ES1). From complementation and maxicell analysis a 58 kd protein was identified as the homolog of protein S1 (RS1). DNA sequence analysis of the R. melilotii rpsA gene identified a protein of 568 amino acids, which showed 47% identical amino acid homology to protein S1 from E. coli. The RS1 protein lacked the two Cys residues which had been reported to play an important role for the function of ES1. Two repeats containing Shine-Dalgarno sequences were identified upstream of the structural gene. Binding studies with RNA polymerase from E. coli and Pseudomonas putida located one RNA-polymerase binding site close to the RS1 gene and another one several hundred basepairs upstream. One possible promoter was also identified by DNA sequence comparison with the corresponding E. coli promoter. Images PMID:3368316

  9. Analysing the New Saturnian Rings, R/2004 S1 and R/2004 S2

    NASA Astrophysics Data System (ADS)

    Winter, S. M. Giuliatti; Sfair, R.; Mourão, D. C.; Bastos, T. A.

    2005-12-01

    The Cassini-Huygens arrival into the Saturnian system brought a large amount of data about the satellites and rings. Two diffuse rings were found in the region between the A ring and Prometheus. R/2004 S1 is coorbital to Atlas and R/2004 S2 is close to Prometheus. In this work we analysed the closest approach between Prometheus and both rings. As a result we found that the satellite removes particles from R/2004 S2 ring. Long-term numerical simulations showed that some particles can cross the F ring region . The well known region of the F ring, where small satellites are present and particles are being taking from the ring, gains a new insight with the presence of particles from R/2004 S2 ring. The computation of the Lyapunov Characteristic Exponent reveled that the R/2004 S2 ring lies in a chaotic region while R/2004 S1 ring and Atlas are in a stable region. Atlas is responsible for the formation of three regimes in the R/2004 S1 ring, as expected for a satellite embedded in a ring.

  10. Sphingosine 1-phosphate protects primary human keratinocytes from apoptosis via nitric oxide formation through the receptor subtype S1P₃.

    PubMed

    Schmitz, Elisabeth I; Potteck, Henrik; Schüppel, Melanie; Manggau, Marianti; Wahydin, Elly; Kleuser, Burkhard

    2012-12-01

    Although the lipid mediator sphingosine 1-phosphate (S1P) has been identified to induce cell growth arrest of human keratinocytes, the sphingolipid effectively protects these epidermal cells from apoptosis. The molecular mechanism of the anti-apoptotic action induced by S1P is less characterized. Apart from S1P, endogenously produced nitric oxide (NO•) has been recognized as a potent modulator of apoptosis in keratinocytes. Therefore, it was of great interest to elucidate whether S1P protects human keratinocytes via a NO•-dependent signalling pathway. Indeed, S1P induced an activation of endothelial nitric oxide synthase (eNOS) in human keratinocytes leading to an enhanced formation of NO•. Most interestingly, the cell protective effect of S1P was almost completely abolished in the presence of the eNOS inhibitor L-NAME as well as in eNOS-deficient keratinocytes indicating that the sphingolipid metabolite S1P protects human keratinocytes from apoptosis via eNOS activation and subsequent production of protective amounts of NO•. It is well established that most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Therefore, the involvement of S1P-receptor subtypes in S1P-mediated eNOS activation has been examined. Indeed, this study clearly shows that the S1P(3) is the exclusive receptor subtype in human keratinocytes which mediates eNOS activation and NO• formation in response to S1P. In congruence, when the S1P(3) receptor subtype is abrogated, S1P almost completely lost its ability to protect human keratinocytes from apoptosis.

  11. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration

    PubMed Central

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter

    2017-01-01

    Introduction. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P1–5) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods. Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results. All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P1. In contrast, M1-polarized macrophages significantly downregulated S1P4. The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion. The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages. PMID:28367448

  12. Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts

    PubMed Central

    Kudo, Masahisa; Yamamoto, Yoshiyuki; Koga, Yoshikatsu; Hamaguchi, Tetsuya; Akimoto, Tetsuo; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-01-01

    Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC-6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S-1 and NC-6004 were compared with those of S-1 and CDDP in a human gastric cancer model. In vitro cytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC-6004 and 5-fluorouracil (5-FU) were compared with the effects of CDDP and 5-FU using the combination index method. The in vivo antitumor effects of S-1/NC-6004 and S-1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, the in vivo antitumor effects did not differ between the S-1/NC-6004 and S-1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S-1/CDDP-treated mice. Our data warrant a clinical evaluation of S-1/NC-6004 combination therapy. PMID:28101359

  13. Assay to measure the secretion of sphingosine-1-phosphate from cells induced by S1P lyase inhibitors.

    PubMed

    Loetscher, Erika; Schneider, Karolina; Beerli, Christian; Billich, Andreas

    2013-04-12

    Inhibitors of the sphingosine-1-phosphate (S1P) degrading enzyme S1P lyase (SPL) may be useful in the therapy of inflammatory diseases by preventing lymphocyte recruitment to diseased tissues. Here we describe a cellular assay for such inhibitors, which takes advantage of the observation that a fraction of the intracellular S1P accumulated in the presence of SPL inhibitors is secreted into the medium of cultured cells. The secreted S1P is then quantified using an S1P-sensitive reporter cell line. In the routine assay protocol, human HEK293T cells are treated with SPL inhibitors in the presence of phosphatase inhibitors and sphingosine; while the phosphatase inhibitors are included to prevent the degradation of S1P secreted from the cells, sphingosine is added as source for intracellular S1P that is prone to SPL degradation. The secreted S1P in the supernatant of the cell cultures is then quantified by measuring calcium flux induced in CHO-K1 cells expressing the human S1P3 receptor. Using this method SPL inhibitors were shown to induce a concentration-dependent increase of extracellular S1P under the conditions used; thus, the assay allows for the ranking of SPL inhibitors according to their potency on living cells.

  14. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

    PubMed

    Kalhori, Veronica; Törnquist, Kid

    2015-03-15

    The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion.

  15. Effect of combined treatment with micelle-incorporated cisplatin (NC-6004) and S-1 on human gastric cancer xenografts.

    PubMed

    Kudo, Masahisa; Yamamoto, Yoshiyuki; Koga, Yoshikatsu; Hamaguchi, Tetsuya; Akimoto, Tetsuo; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-12-01

    Combination therapy with S-1 and cisplatin (CDDP) is the standard chemotherapy for advanced gastric cancer in Japan; however, its administration requires hospitalization for hydration to prevent nephrotoxicity from CDDP. By contrast, NC-6004 appears to reduce the renal toxicity of CDDP and may be used on an outpatient basis. Thus, the effects of combined treatment with S-1 and NC-6004 were compared with those of S-1 and CDDP in a human gastric cancer model. In vitro cytotoxic effects were investigated in 44As3Luc, MKN45 and MKN74 human gastric cancer cell lines. The effects of NC-6004 and 5-fluorouracil (5-FU) were compared with the effects of CDDP and 5-FU using the combination index method. The in vivo antitumor effects of S-1/NC-6004 and S-1/CDDP were evaluated in mice bearing 44As3Luc xenografts. Both combinations exhibited synergistic activity in MKN45 and MKN74 cells and additive effects in 44As3Luc cells. Moreover, the in vivo antitumor effects did not differ between the S-1/NC-6004 and S-1/CDDP treatment groups. However, a significantly lower body weight loss was observed in S-1/NC-6004-treated mice compared with the S-1/CDDP-treated mice. Our data warrant a clinical evaluation of S-1/NC-6004 combination therapy.

  16. Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction

    PubMed Central

    Sanna, M. Germana; Vincent, Kevin P.; Repetto, Emanuela; Nguyen, Nhan; Brown, Steven J.; Abgaryan, Lusine; Riley, Sean W.; Leaf, Nora B.; Cahalan, Stuart M.; Kiosses, William B.; Kohno, Yasushi; Brown, Joan Heller; McCulloch, Andrew D.

    2016-01-01

    The molecular pharmacology of the G protein–coupled receptors for sphingosine 1-phosphate (S1P) provides important insight into established and new therapeutic targets. A new, potent bitopic S1P3 antagonist, SPM-354, with in vivo activity, has been used, together with S1P3-knockin and S1P3-knockout mice to define the spatial and functional properties of S1P3 in regulating cardiac conduction. We show that S1P3 is a key direct regulator of cardiac rhythm both in vivo and in isolated perfused hearts. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in vivo and S1P in isolated hearts induced a spectrum of cardiac effects, ranging from sinus bradycardia to complete heart block, as measured by a surface electrocardiogram in anesthetized mice and in volume-conducted Langendorff preparations. The agonist effects on complete heart block are absent in S1P3-knockout mice and are reversed in wild-type mice with SPM-354, as characterized and described here. Homologous knockin of S1P3-mCherry is fully functional pharmacologically and is strongly expressed by immunohistochemistry confocal microscopy in Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4 (HCN4)-positive atrioventricular node and His-Purkinje fibers, with relative less expression in the HCN4-positive sinoatrial node. In Langendorff studies, at constant pressure, SPM-354 restored sinus rhythm in S1P-induced complete heart block and fully reversed S1P-mediated bradycardia. S1P3 distribution and function in the mouse ventricular cardiac conduction system suggest a direct mechanism for heart block risk that should be further studied in humans. A richer understanding of receptor and ligand usage in the pacemaker cells of the cardiac system is likely to be useful in understanding ventricular conduction in health, disease, and pharmacology. PMID:26494861

  17. Unusual Water Production Activity of Comet C/2012 S1 (ISON): Outbursts and Continuous Fragmentation

    NASA Astrophysics Data System (ADS)

    Combi, M. R.; Fougere, N.; Mäkinen, J. T. T.; Bertaux, J.-L.; Quémerais, E.; Ferron, S.

    2014-06-01

    The Solar Wind ANisotropies (SWAN) all-sky hydrogen Lyα camera on the SOlar and Heliospheric Observer (SOHO) satellite observed the hydrogen coma of comet C/2012 S1 (ISON) for most of the last month of its activity from 2013 October 24 to November 24, ending just 4 days before perihelion and its final disruption. The water production rate of the comet was determined from these observations. SOHO has been operating in a halo orbit around the Earth-Sun L1 Lagrange point since its launch in late 1995. Most water vapor produced by comets is ultimately photodissociated into two H atoms and one O atom producing a huge hydrogen coma that is routinely observed in the daily SWAN images in comets of sufficient brightness. Water production rates were calculated from 22 images over most of the last month of the pre-perihelion apparition. The water production rate increased very slowly on average from October 24.9 until November 12.9, staying between 1.8 and 3.4 × 1028 s-1, after which it increased dramatically, reaching 1.6 to 2 × 1030 s-1 from November 21.6 to 23.6. It was not detected after perihelion on December 3.7 when it should have been visible. We examine the active surface area necessary to explain the water production rate and its variation and are able to place constraints on the physical size of the original nucleus necessary to account for the large amount of activity from November 12.9 and until just before perihelion.

  18. Synchronous basin-wide Mediterranean Sapropel S1 formation; Preservation versus Productivity

    NASA Astrophysics Data System (ADS)

    De Lange, Gert J.; Slomp, Caroline; Corselli, Cesare; Erba, Elisabetta; Thomson, John; Reitz, Anja

    2013-04-01

    The timing of deposition of all distinct organic-rich units (sapropels) in eastern Mediterraneran sediments is precession-related and is associated with humid climate conditions. The last of such 'humid periods' occurred from 11 - 5 kyr 14C ago, simultaneous with a sustained circum-Mediterranean wet period including a vegetated Sahara. The end of this period coincides with a high manganese-oxide peak in all 30 studied cores and concurs with an abrupt re-ventilation event at 5.7 kyr for the deep-water. We demonstrate that the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1 formation (De Lange ea., 2008). This has resulted in a differential basin-wide preservation of S1 determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. Climate-induced stratification of the ocean may thus contribute to enhanced preservation of organic matter, i.e. formation of sapropels (and potentially black shales). Reference De Lange G.J., Thomson J., Reitz A., Slomp C.P., Principato M.S., Erba E., and Corselli C. (2008) Synchronous basin-wide formation and redox-controlled preservation of a Mediterranean sapropel. Nature Geo 1, 606-610.

  19. Experimental design and environmental parameters affect Rhodospirillum rubrum S1H response to space flight.

    PubMed

    Mastroleo, Felice; Van Houdt, Rob; Leroy, Baptiste; Benotmane, M Abderrafi; Janssen, Ann; Mergeay, Max; Vanhavere, Filip; Hendrickx, Larissa; Wattiez, Ruddy; Leys, Natalie

    2009-12-01

    In view of long-haul space exploration missions, the European Space Agency initiated the Micro-Ecological Life Support System Alternative (MELiSSA) project targeting the total recycling of organic waste produced by the astronauts into oxygen, water and food using a loop of bacterial and higher plant bioreactors. In that purpose, the alpha-proteobacterium, Rhodospirillum rubrum S1H, was sent twice to the International Space Station and was analyzed post-flight using a newly developed R. rubrum whole genome oligonucleotide microarray and high throughput gel-free proteomics with Isotope-Coded Protein Label technology. Moreover, in an effort to identify a specific response of R. rubrum S1H to space flight, simulation of microgravity and space-ionizing radiation were performed on Earth under identical culture set-up and growth conditions as encountered during the actual space journeys. Transcriptomic and proteomic data were integrated and permitted to put forward the importance of medium composition and culture set-up on the response of the bacterium to space flight-related environmental conditions. In addition, we showed for the first time that a low dose of ionizing radiation (2 mGy) can induce a significant response at the transcriptomic level, although no change in cell viability and only a few significant differentially expressed proteins were observed. From the MELiSSA perspective, we could argue the effect of microgravity to be minimized, whereas R. rubrum S1H could be more sensitive to ionizing radiation during long-term space exploration mission.

  20. Source and development of large manganese enrichments above eastern Mediterranean sapropel S1

    NASA Astrophysics Data System (ADS)

    Reitz, Anja; Thomson, John; de Lange, Gert J.; Hensen, Christian

    2006-09-01

    The residual dark unit of the most recent eastern Mediterranean sapropel (S1) is usually overlain by sediments with enhanced concentrations of MnOx in two separated layers. The variability and magnitude of the Mn enrichment at different locations and water depths indicate that Mn must have been added preferentially to sediments at intermediate (1-2 km) water depths. We propose a two-stage mechanism for the Mn enrichment that involves decreasing oxygenation with increasing water depth. This mechanism involves the loss of reduced Mn2+ from the deepest sediments (>2 km water depth) into overlying anoxic waters and a variable gain of MnOx in sediments in contact with oxygenated waters at shallower depth. In the S1 unit that receives the extra MnOx input, an upper higher Mn-enriched zone (>3 wt %) is maintained continuously at the top of the accumulating S1 unit because the pore waters are anoxic at shallow sediment depth while bottom waters are oxic to some degree. In a reactive-transport model, the Mn enrichment in the upper zone could not be supported by normal sediment diagenesis. Thus the MnOx in the upper Mn horizon must have formed mainly in the water column. The MnOx in the upper Mn-enriched zone adsorbed Mo and Li from seawater in a similar manner as other Mn-enriched oxic sediments, nodules, and crusts, with a Mn:Mo ratio of ˜600:1, a Mn:Li ratio of ˜750:1, and a δ98/95MoMOMO of -2.5 ‰.

  1. Numerical modeling of the oceanic S1 tide for Earth rotation studies

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Einspigel, David

    2015-04-01

    Diurnal S1 oceanic oscillations induced by atmospheric pressure loading elicit small but measurable perturbations of universal time, polar motion, and the prograde annual component of nutation. In a priori models of Earth rotation variations, these signals are as-yet unconsidered'partly due to the fact that the underlying globally-gridded S1 harmonics can only be inferred from purely hydrodynamic ocean models which lack the reliable elevation constraints from satellite altimetry. Such free-running forward integrations of the shallow water equations usually overestimate tidal energies and therefore also OAM (oceanic angular momentum), unless the model formulation allows for significant dissipation in the deep ocean. For practical purposes, abyssal energy flux and hence the accuracy of tidal elevations can be controlled by a tunable but inordinately high viscosity value or by evoking additional quadratic wave drag when surface heights change rapidly. A third and physically plausible modeling route is to parametrize the sub-grid scale conversion of barotropic currents into small internal tides by aid of a linear drag term. In the present paper, we study the impact of these different dissipation schemes on the fidelity of surface elevations in a simple barotropic time-stepping model forced by selected gravitational equilibrium tides as well as diurnal air pressure variations. After determining the optimal drag formulation through validation runs with the well-known principal gravitational K1 tide, the OAM values for each of the hydrodynamic S1 solutions are documented and discussed in the specific context of their contribution to the prograde annual signal in Earth's nutation.

  2. Odin observations of ammonia in the Sgr A +50 km s-1 cloud and circumnuclear disk

    NASA Astrophysics Data System (ADS)

    Sandqvist, Aa.; Hjalmarson, Å.; Frisk, U.; Lundin, S.; Nordh, L.; Olberg, M.; Olofsson, G.

    2017-03-01

    Context. The Odin satellite is now into its sixteenth year of operation, much surpassing its design life of two years. One of the sources which Odin has observed in great detail is the Sgr A complex in the centre of the Milky Way. Aims: To study the presence of NH3 in the Galactic centre and spiral arms. Methods: Recently, Odin has made complementary observations of the 572 GHz NH3 line towards the Sgr A +50 km s-1 cloud and circumnuclear disk (CND). Results: Significant NH3 emission has been observed in both the +50 km s-1 cloud and the CND. Clear NH3 absorption has also been detected in many of the spiral arm features along the line of sight from the Sun to the core of our Galaxy. Conclusions: The very large velocity width (80 km s-1) of the NH3 emission associated with the shock region in the southwestern part of the CND may suggest a formation/desorption scenario similar to that of gas-phase H2O in shocks/outflows. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), the Centre National d'Études Spatiales (CNES), France, and the European Space Agency (ESA). The former Space division of the Swedish Space Corporation, today OHB Sweden, is the prime contractor, also responsible for Odin operations.The reduced spectra are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/599/A135

  3. Cloning and characterization of monofunctional catalase from photosynthetic bacterium Rhodospirillum rubrum S1.

    PubMed

    Lee, Dong-Heon; Oh, Duck-Chul; Oh, You-Sung; Malinverni, Juliana C; Kukor, Jerome J; Kahng, Hyung-Yeel

    2007-09-01

    In this study, an approx. 2.5-kb gene fragment including the catalase gene from Rhodospirillum rubrum S1 was cloned and characterized. The determination of the complete nucleotide sequence revealed that the cloned DNA fragment was organized into three open reading frames, designated as ORF1, catalase, and ORF3 in that order. The catalase gene consisted of 1,455 nucleotides and 484 amino acids, including the initiation and stop codons, and was located 326 bp upstream in the opposite direction of ORF1. The catalase was overproduced in Escherichia coli UM255, a catalase-deficient mutant, and then purified for the biochemical characterization of the enzyme. The purified catalase had an estimated molecular mass of 189 kDa, consisting of four identical subunits of 61 kDa. The enzyme exhibited activity over a broad pH range from pH 5.0 to pH 11.0 and temperature range from 20 degrees C to 60 degrees C. The catalase activity was inhibited by 3-amino-1,2,4-triazole, cyanide, azide, and hydroxylamine. The enzyme's K(m) value and V(max) of the catalase for H2O2 were 21.8 mM and 39,960 U/mg, respectively. Spectrophotometric analysis revealed that the ratio of A406 to A280 for the catalase was 0.97, indicating the presence of a ferric component. The absorption spectrum of catalase-4 exhibited a Soret band at 406 nm, which is typical of a heme-containing catalase. Treatment of the enzyme with dithionite did not alter the spectral shape and revealed no peroxidase activity. The combined results of the gene sequence and biochemical characterization proved that the catalase cloned from strain S1in this study was a typical monofunctional catalase, which differed from the other types of catalases found in strain S1.

  4. Toxicogenomic Response of Rhodospirillum rubrum S1H to the Micropollutant Triclosan▿

    PubMed Central

    Pycke, Benny F. G.; Vanermen, Guido; Monsieurs, Pieter; De Wever, Heleen; Mergeay, Max; Verstraete, Willy; Leys, Natalie

    2010-01-01

    In the framework of the Micro-Ecological Life Support System Alternative (MELiSSA) project, a pilot study was performed to identify the effects of triclosan on the MELiSSA carbon-mineralizing microorganism Rhodospirillum rubrum S1H. Triclosan is a biocide that is commonly found in human excrement and is considered an emerging pollutant in wastewater and the environment. Chronic exposure to MELiSSA-relevant concentrations (≥25 μg liter−1) of triclosan resulted in a significant extension of the lag phase of this organism but hardly affected the growth rate. Analytical determinations gave no indication of triclosan biodegradation during the growth experiment, and flow cytometric viability analyses revealed that triclosan is bacteriostatic and only slightly toxic to R. rubrum S1H. Using microarray analyses, the genetic mechanisms supporting the reversibility of triclosan-induced inhibition were scrutinized. An extremely triclosan-responsive cluster of four small adjacent genes was identified, for which there was up to 34-fold induction with 25 μg liter−1 triclosan. These four genes, for which the designation muf (micropollutant-upregulated factor) is proposed, appear to be unique to R. rubrum and are shown here for the first time to be involved in the response to stress. Moreover, numerous other systems that are associated with the proton motive force were shown to be responsive to triclosan, but they were never as highly upregulated as the muf genes. In response to triclosan, R. rubrum S1H induced transcription of the phage shock protein operon (pspABC), numerous efflux systems, cell envelope consolidation mechanisms, the oxidative stress response, beta-oxidation, and carbonic anhydrase, while there was downregulation of bacterial conjugation and carboxysome synthesis genes. The muf genes and three efflux-related genes showed the most potential to be low-dose biomarkers. PMID:20363786

  5. Properties of digital 1/3-octave filters implemented according to ANSI S1.11

    NASA Astrophysics Data System (ADS)

    Geras, Antonina; Starecki, Tomasz

    The paper presents results of investigation into properties of digital filters implemented in compliance with ANSI S1.11 Standard: Octave-Band and Fractional-Octave Band Analog and Digital Filters. The discussed solutions are digital one-third-octave IIR filters with Direct Form I topology. Performed simulations showed that the filters exhibit strong problems with stability, especially in the case of low center frequency filters. Another problem clearly visible in all investigated structures was poor attenuation at the frequencies above the passband. Although the filters were implemented according to the ANSI standard, none of them met all of the requirements of the standard.

  6. Observation of an Exotic S = +1 Baryon in Exclusive Photoproduction from the Deuteron

    SciTech Connect

    Stepan Stepanyan; Kenneth Hicks; Daniel Carman; Evgueni Pasyuk; Reinhard Schumacher; Elton Smith; David Tedeschi; Luminita Todor

    2003-12-19

    In an exclusive measurement of the reaction {gamma}d {yields} K{sup +} K{sup -} p n, a narrow peak that can be attributed to an exotic baryon with strangeness S = +1 is seen in the K{sup +}n invariant mass spectrum. The peak is at 1542 {+-} 5 MeV/c{sup 2} with a measured width of 21 MeV/c{sup 2} FWHM, equivalent to the experimental invariant mass resolution. The statistical significance of the peak is 5.3 {+-} 0.5 {sigma} for a Gaussian peak shape on top of a smooth background.

  7. Mechanisms for spin supersolidity in S=(1/2) spin-dimer antiferromagnets

    SciTech Connect

    Picon, J.-D.; Albuquerque, A. F.; Schmidt, K. P.; Laflorencie, N.; Troyer, M.; Mila, F.

    2008-11-01

    Using perturbative expansions and the contractor renormalization (CORE) algorithm, we obtain effective hard-core bosonic Hamiltonians describing the low-energy physics of S=1/2 spin-dimer antiferromagnets known to display supersolid phases under an applied magnetic field. The resulting effective models are investigated by means of mean-field analysis and quantum Monte Carlo simulations. A 'leapfrog mechanism,' through means of which extra singlets delocalize in a checkerboard-solid environment via correlated hoppings, is unveiled that accounts for the supersolid behavior.

  8. Strangeness S =-1 hyperon-nucleon scattering in covariant chiral effective field theory

    NASA Astrophysics Data System (ADS)

    Li, Kai-Wen; Ren, Xiu-Lei; Geng, Li-Sheng; Long, Bingwei

    2016-07-01

    Motivated by the successes of covariant baryon chiral perturbation theory in one-baryon systems and in heavy-light systems, we study relevance of relativistic effects in hyperon-nucleon interactions with strangeness S =-1 . In this exploratory work, we follow the covariant framework developed by Epelbaum and Gegelia to calculate the Y N scattering amplitude at leading order. By fitting the five low-energy constants to the experimental data, we find that the cutoff dependence is mitigated, compared with the heavy-baryon approach. Nevertheless, the description of the experimental data remains quantitatively similar at leading order.

  9. SU(2s+1) symmetry and nonlinear dynamics of high spin magnets

    SciTech Connect

    Kovalevsky, M.Y. Glushchenko, A.V.

    2014-10-15

    The article is devoted to the description of dynamics of magnets with arbitrary spin on the basis of the Hamiltonian formalism. The relationship of quantum states and magnetic degrees of freedom has been considered. Subalgebras of Poisson bracket of magnetic values for spin s=1/2; 1; 3/2 have been established. We have obtained non-linear dynamic equations for the normal and degenerate non-equilibrium states of high-spin magnets with the SO(3), SU(4), SU(2)×SU(2), SU(3), SO(4), SO(5) symmetries of exchange interaction. The connection between models of magnetic exchange energy and the Casimir invariants has been discussed.

  10. φ meson production frompbar p collisions atsqrt s = 1.8 TeV

    NASA Astrophysics Data System (ADS)

    Alexopoulos, T.; Allen, C.; Anderson, E. W.; Balamurali, V.; Banerjee, S.; Beery, P. D.; Bhat, P.; Bishop, J. M.; Biswas, N. N.; Bujak, A.; Carmony, D. D.; Carter, T.; Cole, P.; Choi, Y.; Debonte, R.; Decarlo, V.; Erwin, A. R.; Findeisen, C.; Goshaw, A. T.; Gutay, L. J.; Hirsch, A. S.; Hojvat, C.; Jennings, J. R.; Kenney, V. P.; Lindsey, C. S.; Loomis, C.; Losecco, J. M.; McMahon, T.; McManus, A. P.; Morgan, N.; Nelson, K.; Oh, S. H.; Porile, N. T.; Rimai, A.; Reeves, D.; Robertson, W. J.; Scharenberg, R. P.; Stringfellow, B. C.; Stampke, S. R.; Thompson, M.; Turkot, F.; Walker, W. D.; Wang, C. H.; Warchol, J.; Wesson, D. K.; Zhan, Y.

    1995-09-01

    Fermilab experiment E735 located at the CO intersection region of thesqrt s = 1.8 TeVpbar p collider analysed over 900 Φ→ K + K - events. Measured were the transverse momentum spectrum, the correlation between the average transverse momentum < pt> and the charged particle multiphcity N c , as well as the probability of Φ production per charged track, N Φ / N c , versus N c . We have also made an estinate of the total inclusive cross section for Φ mesons,σ (pbar p to φ X) = 7.3 ± 2.2 mb.

  11. Amplification of S-1 Spheromak current by an inductive current transformer

    SciTech Connect

    Jardin, S.C.; Janos, A.; Yamada, M.

    1985-11-01

    We attempt to predict the consequences of adding an inductive current transformer (OH Transformer) to the present S-1 Spheromak experiment. Axisymmetric modeling with only classical dissipation shows an increase of toroidal current and a shrinking and hollowing of the current channel, conserving toroidal flux. These unstable profiles will undergo helical reconnection, conserving helicity K = ..integral.. A-vector x B-vector d tau while increasing the toroidal flux and decreasing the poloidal flux so that the plasma relaxes toward the Taylor state. This flux rearrangement is modeled by a new current viscosity term in the mean-field Ohm's law which conserves helicity and dissipates energy.

  12. QCD Results from the CDF Experiment at squareroot s = 1.96 TeV

    SciTech Connect

    Michele Gallinaro

    2003-05-19

    First QCD results obtained from the CDF experiment using Run II data are reported. The Run II physics program at the Tevatron started in the spring of 2001, with protons and anti-protons colliding at an energy of {radical}s = 1.96 TeV. The size of the data sample already compares to that of Run I. Results presented here include the measurement of the inclusive jet cross section, a search for new particles decaying to dijets, and a study of diffractive dijet events.

  13. Exciton mobility edge in CdS 1-xSe x solid solutions

    NASA Astrophysics Data System (ADS)

    Permogorov, S.; Reznitsky, A.; Verbin, S.; Lysenko, V.

    1983-07-01

    Low temperature emission spectra of localized excitons in CdS 1-xSe x solid solutions under the monochromatic excitation with tunable laser have been studied. It has been found that the luminescence of localized excitons has a high degree of linear polarization with respect to the polarization direction of exciting light. This polarization reflects the "hidden" anisotropy of macroscopically isotropic localized exciton system and strongly depends on the frequency of exciting light. Study of this dependence has permitted for the first time a determination of position of the "mobility edge" for exciton migration in disordered semiconductor solid solution.

  14. Redox-Controled Preservation of Mediterranean Sapropel S1 deposits during Formation and Interruption

    NASA Astrophysics Data System (ADS)

    De Lange, Gert J.; Filippidi, Amalia; Goudeau, Marie-Louise; Hennekam, Rick

    2016-04-01

    Organic-rich units (sapropels) occur in Mediterraneran sediments in a repetitive, climate-controled way. Their deposition is thought to be precession-related and to be associated with humid climate conditions. The last humid period from 11 - 5 kyr 14C ago, occurred simultaneous with a sustained circum-Mediterranean wet period and vegetated Sahara. Within that period, the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1 formation. This has resulted in a differential basin-wide preservation of S1sediments determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. The end of this period is marked by a basin-wide high sedimentary manganese-oxide peak that represents an abrupt re-ventilation of the deep-water at 5.7 kyr. The sustaining oxic conditions thereafter have resulted in a downward progressing oxidation-front that is not only characterized by the degradation of most organic matter over its active pathway, but also by the built-up of manganese oxide. The latter has resulted in a secondary diagenetic Mn-peak below the first, upper, ventilation Mn-peak. Apart from the major re-ventilation event at the end of sapropel S1 formation, also other, short-term ventilation events appear to have occurred during its formation, notably during the 8.2 ka event. This potentially basin-wide event is particularly noticeable at relatively shallow near-coastal sites of high sedimentation rates. It marks a brief episode of not only re-oxygenated deep water thus reduced preservation, but also decreased primary productivity thus nutrient supply. This 8.2 cal ka BP interruption event is thought to be related to enhanced deep water formation

  15. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor

    SciTech Connect

    Maize, Kimberly M.; Kurbanov, Elbek K.; Johnson, Rodney L.; Amin, Elizabeth Ambrose; Finzel, Barry C.

    2016-07-05

    The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1'* which might afford new opportunities to design selective inhibitors that target this subsite.

  16. Phospholipid transfer protein deficiency decreases the content of S1P in HDL via the loss of its transfer capability.

    PubMed

    Yu, Yang; Guo, Shoudong; Feng, Yumei; Feng, Lei; Cui, Yingjie; Song, Guohua; Luo, Tian; Zhang, Ke; Wang, Yiwei; Jiang, Xian-Cheng; Qin, Shucun

    2014-02-01

    Sphingosine-1-phosphate (S1P) is an amphiphilic signaling molecule, which is enriched in functional high density lipoprotein (HDL) and shows arterial protection. The distribution of S1P is changed with increased plasma phospholipid transfer protein (PLTP) activity and impaired HDL function in patients with coronary heart diseases. Therefore, we hypothesized that PLTP might transfer S1P among cells or lipoproteins. We found that plasma S1P contents were decreased by 60.1 % in PLTP knockout mice (PLTP-/-, N = 5) compared with their wild type littermates (WT, N = 5) (151.70 ± 38.59 vs. 379.32 ± 59.90 nmol/l, P<0.01). S1P content in HDL fraction (HDL-S1P) from PLTP-/- was decreased by 64.7 % compared with WT (49.36 ± 1.49 vs. 139.76 ± 2.94 nmol/l, P<0.01). The results of the S1P transfer assay indicated that PLTP could facilitate S1P transport from erythrocytes to HDL at 37 °C in D-Hanks buffer. Plasma content of apolipoprotein M, a specific adaptor of S1P, was not changed in PLTP-/- compared with WT. Therefore, we concluded that PLTP was a key factor to maintain plasma HDL-S1P, and PLTP deficiency could decrease the S1P content in plasma lipoproteins, which involves its capability of transferring S1P from erythrocyte to HDL.

  17. ClpS1 Is a Conserved Substrate Selector for the Chloroplast Clp Protease System in Arabidopsis[C][W

    PubMed Central

    Nishimura, Kenji; Asakura, Yukari; Friso, Giulia; Kim, Jitae; Oh, Soo-hyun; Rutschow, Heidi; Ponnala, Lalit; van Wijk, Klaas J.

    2013-01-01

    Whereas the plastid caseinolytic peptidase (Clp) P protease system is essential for plant development, substrates and substrate selection mechanisms are unknown. Bacterial ClpS is involved in N-degron substrate selection and delivery to the ClpAP protease. Through phylogenetic analysis, we show that all angiosperms contain ClpS1 and some species also contain ClpS1-like protein(s). In silico analysis suggests that ClpS1 is the functional homolog of bacterial ClpS. We show that Arabidopsis thaliana ClpS1 interacts with plastid ClpC1,2 chaperones. The Arabidopsis ClpS1 null mutant (clps1) lacks a visible phenotype, and no genetic interactions with ClpC/D chaperone or ClpPR core mutants were observed. However, clps1, but not clpc1-1, has increased sensitivity to the translational elongation inhibitor chloramphenicol suggesting a link between translational capacity and ClpS1. Moreover, ClpS1 was upregulated in clpc1-1, and quantitative proteomics of clps1, clpc1, and clps1 clpc1 showed specific molecular phenotypes attributed to loss of ClpC1 or ClpS1. In particular, clps1 showed alteration of the tetrapyrrole pathway. Affinity purification identified eight candidate ClpS1 substrates, including plastid DNA repair proteins and Glu tRNA reductase, which is a control point for tetrapyrrole synthesis. ClpS1 interaction with five substrates strictly depended on two conserved ClpS1 residues involved in N-degron recognition. ClpS1 function, substrates, and substrate recognition mechanisms are discussed. PMID:23898032

  18. Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.

    PubMed

    Loh, Kenneth C; Leong, Weng-In; Carlson, Morgan E; Oskouian, Babak; Kumar, Ashok; Fyrst, Henrik; Zhang, Meng; Proia, Richard L; Hoffman, Eric P; Saba, Julie D

    2012-01-01

    Sphingosine-1-phosphate (S1P) activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs) through unknown mechanisms. Here we show that muscle injury induces dynamic changes in S1P signaling and metabolism in vivo. These changes include early and profound induction of the gene encoding the S1P biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme sphingosine phosphate lyase (SPL) 3 days later. These changes correlate with a transient increase in circulating S1P levels after muscle injury. We show a specific requirement for SphK1 to support efficient muscle regeneration and SC proliferation and differentiation. Mdx mice, which serve as a model for muscular dystrophy (MD), were found to be S1P-deficient and exhibited muscle SPL upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle. Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2)-dependent inhibition of Rac1, thereby activating Signal Transducer and Activator of Transcription 3 (STAT3), a central player in inflammatory signaling. STAT3 activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in myoblasts. Our findings suggest that S1P promotes SC progression through the cell cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling and that SPL inhibition may provide a therapeutic strategy for MD.

  19. The effect of low levels of lead (Pb) in the blood on levels of sphingosine-1-phosphate (S1P) and expression of S1P receptor 1 in the brain of the rat in the perinatal period.

    PubMed

    Łukomska, A; Baranowska-Bosiacka, I; Budkowska, M; Pilutin, A; Tarnowski, M; Dec, K; Dołęgowska, B; Metryka, E; Chlubek, D; Gutowska, I

    2017-01-01

    Sphingolipids are the main components of the lipid membrane. They also perform structural functions and participate in many signal transmission processes. One of the bioactive sphingolipids is sphingosine-1-phosphate (S1P), a ligand for five G protein-coupled receptors (S1PRs1-5), which can also act as an intracellular second messenger. S1P is responsible for the stimulation of progenitor cells in the brain, but it can also induce apoptosis of mature neurons. This study is aimed at assessing the effect of pre- and neonatal exposure to permissible Pb concentrations on S1P levels and S1PR1 (EDG1) expression in the prefrontal cortex, cerebellum, and hippocampus of rats. The concentrations of S1P were determined by RP-HPLC, S1PR1 expression was determined by RT PCR and Western Blot, and receptor immunolocalization was determined by immunohistochemistry method. Our results showed that even low blood Pb concentrations, i.e. within the acceptable limit of 10 μg/dL caused changes in the concentration of S1P in the cerebellum, prefrontal cortex, and hippocampus. Our data also showed a significant decrease in the level of S1PR1 in all studied part of brain, without significant changes in S1PR1 gene expression. Pre- and neonatal exposure to Pb also resulted in a decrease in the expression of S1PR1 in glial cells in all regions of the Cornu Ammonis (CA1-CA4) and Dentate Gyrus in the hippocampus, as well as in all layers of the cerebellum and prefrontal cortex, compared to the unexposed control group.

  20. Sphingosine-1-phosphate (S1P): A Potential Biomarker and Therapeutic Target for Endothelial Dysfunction and Sepsis?

    PubMed

    Winkler, Martin S; Nierhaus, Axel; Poppe, Annika; Greiwe, Gillis; Gräler, Markus; Daum, Guenter

    2016-12-02

    Sepsis is an acute life-threatening multiple organ failure caused by a dysregulated host response to infection. Endothelial dysfunction, particularly barrier disruption leading to increased vascular permeability, edema and insufficient tissue oxygenation is critical to sepsis pathogenesis. Sphingosine-1-phosphate (S1P) is a signaling lipid that regulates important pathophysiological processes including vascular endothelial cell permeability, inflammation and coagulation. It is present at high concentrations in blood and lymph and at very low concentrations in tissues due to the activity of the S1P-degrading enzyme S1P-lyase in tissue cells. Recently, four preclinical observational studies determined S1P levels in serum or plasma of sepsis patients, and all found reduced S1P levels associated with the disease. Based on these findings, this review summarizes S1P-regulated processes pertaining to endothelial functions, discusses the possible use of S1P as a marker and possibilities how to manipulate S1P levels and S1P receptor activation to restore endothelial integrity, dampen the inflammatory host response, and improve organ function in sepsis.

  1. Dynamics of vibrational relaxation in the S 1 state of carotenoids having 11 conjugated CC bonds

    NASA Astrophysics Data System (ADS)

    Hörvin Billsten, Helena; Zigmantas, Donatas; Sundström, Villy; Polívka, Tomáš

    2002-04-01

    Transient absorption spectra and kinetics in the 470-650 nm region were recorded for lycopene, β-carotene and zeaxanthin, all carotenoids with 11 conjugated double bonds, in two solvents with different polarity. Analysis of the red wing of the carotenoid S 1-S n transition revealed presence of a pronounced shoulder at early delay times. The kinetics recorded at this low-energy shoulder of the S 1-S n transition yields an additional decay component of 500-800 fs in addition to the main S 1 decay. This dynamics is ascribed to a vibrational relaxation in the S 1 state of the carotenoids.

  2. T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow

    PubMed Central

    Jenne, Craig N.; Enders, Anselm; Rivera, Richard; Watson, Susan R.; Bankovich, Alexander J.; Pereira, Joao P.; Xu, Ying; Roots, Carla M.; Beilke, Joshua N.; Banerjee, Arnob; Reiner, Steven L.; Miller, Sara A.; Weinmann, Amy S.; Goodnow, Chris C.

    2009-01-01

    During a screen for ethylnitrosourea-induced mutations in mice affecting blood natural killer (NK) cells, we identified a strain, designated Duane, in which NK cells were reduced in blood and spleen but increased in lymph nodes (LNs) and bone marrow (BM). The accumulation of NK cells in LNs reflected a decreased ability to exit into lymph. This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein. Duane NK cells have a 30-fold deficiency in sphingosine-1-phosphate receptor 5 (S1P5) transcript levels, and S1P5-deficient mice exhibit an egress defect similar to Duane. Chromatin immunoprecipitation confirms binding of T-bet to the S1pr5 locus. S1P-deficient mice exhibit a more severe NK cell egress block, and the FTY720-sensitive S1P1 also plays a role in NK cell egress from LNs. S1P5 is not inhibited by CD69, a property that may facilitate trafficking of activated NK cells to effector sites. Finally, the accumulation of NK cells within BM of S1P-deficient mice was associated with reduced numbers in BM sinusoids, suggesting a role for S1P in BM egress. In summary, these findings identify S1P5 as a T-bet–induced gene that is required for NK cell egress from LNs and BM. PMID:19808259

  3. Protein crystallography beamline BL2S1 at the Aichi synchrotron

    SciTech Connect

    Watanabe, Nobuhisa; Nagae, Takayuki; Yamada, Yusuke; Tomita, Ayana; Matsugaki, Naohiro; Tabuchi, Masao

    2017-01-01

    The protein crystallography beamline BL2S1, constructed at one of the 5 T superconducting bending-magnet ports of the Aichi synchrotron, is available to users associated with academic and industrial organizations. The beamline is mainly intended for use in X-ray diffraction measurements of single-crystals of macromolecules such as proteins and nucleic acids. Diffraction measurements for crystals of other materials are also possible, such as inorganic and organic compounds. BL2S1 covers the energy range 7–17 keV (1.8–0.7 Å) with an asymmetric-cut curved single-crystal monochromator [Ge(111) or Ge(220)], and a platinum-coated Si mirror is used for vertical focusing and as a higher-order cutoff filter. The beamline is equipped with a single-axis goniometer, a CCD detector, and an open-flow cryogenic sample cooler. Lastly, high-pressure protein crystallography with a diamond anvil cell can also be performed using this beamline.

  4. S1 gene-based phylogeny of infectious bronchitis virus: An attempt to harmonize virus classification.

    PubMed

    Valastro, Viviana; Holmes, Edward C; Britton, Paul; Fusaro, Alice; Jackwood, Mark W; Cattoli, Giovanni; Monne, Isabella

    2016-04-01

    Infectious bronchitis virus (IBV) is the causative agent of a highly contagious disease that results in severe economic losses to the global poultry industry. The virus exists in a wide variety of genetically distinct viral types, and both phylogenetic analysis and measures of pairwise similarity among nucleotide or amino acid sequences have been used to classify IBV strains. However, there is currently no consensus on the method by which IBV sequences should be compared, and heterogeneous genetic group designations that are inconsistent with phylogenetic history have been adopted, leading to the confusing coexistence of multiple genotyping schemes. Herein, we propose a simple and repeatable phylogeny-based classification system combined with an unambiguous and rationale lineage nomenclature for the assignment of IBV strains. By using complete nucleotide sequences of the S1 gene we determined the phylogenetic structure of IBV, which in turn allowed us to define 6 genotypes that together comprise 32 distinct viral lineages and a number of inter-lineage recombinants. Because of extensive rate variation among IBVs, we suggest that the inference of phylogenetic relationships alone represents a more appropriate criterion for sequence classification than pairwise sequence comparisons. The adoption of an internationally accepted viral nomenclature is crucial for future studies of IBV epidemiology and evolution, and the classification scheme presented here can be updated and revised novel S1 sequences should become available.

  5. Quantum vs Classical Magnetization Plateaus of S=1/2 Frustrated Heisenberg Chains

    NASA Astrophysics Data System (ADS)

    Hida, Kazuo; Affleck, Ian

    2005-06-01

    The competition between quantum and classical magnetization plateaus of S=1/2 frustrated Heisenberg chains with modified exchange couplings is investigated. The conventional S=1/2 frustrated Heisenberg chain is known to exhibit a 3-fold degenerate \\uparrow\\downarrow\\uparrow-type classical plateau at 1/3 of the saturation magnetization accompanied by the spontaneous Z3 translational symmetry breakdown. The stability of this plateau phase against period 3 exchange modulation which favors the \\bullet\\hskip -1pt-\\hskip -1pt\\bullet \\uparrow-type quantum plateau state (\\bullet\\hskip -1pt-\\hskip -1pt\\bullet = singlet dimer) is studied by bosonization, renormalization group and numerical diagonalization methods. The ground state phase diagram and the spin configuration in each phase are numerically determined. The translationally invariant Valence Bond Solid-type model with 4-spin and third neighbor interactions, which has the exact \\bullet\\hskip -1pt-\\hskip -1pt\\bullet \\uparrow-type quantum plateau state, is also presented. The phase transition to the classical \\uparrow\\downarrow\\uparrow-type ground state is also observed by varying the strength of 4-spin and third neighbor interactions. The relation between these two types of models with quantum plateau states is discussed.

  6. Synthesis, characterization and chemical stability of silicon dichalcogenides, Si(SexS1-x)2

    NASA Astrophysics Data System (ADS)

    Chen, Chen; Zhang, Xiaotian; Krishna, Lakshmi; Kendrick, Chito; Shang, Shun-Li; Toberer, Eric; Liu, Zi-Kui; Tamboli, Adele; Redwing, Joan M.

    2016-10-01

    Silicon dichalcogenides have an intriguing crystal structure consisting of long tetrahedral chains held together by van der Waals forces but the electronic and optical properties have been less explored. In the present work, bulk SiSe2, SiS2, and Si(SexS1-x)2 were synthesized by the congruent melt growth method and characterized by Raman spectroscopy, X-ray Diffraction and UV/visible/IR transmission measurements supported by first-principles calculations. First-principles calculations reveal a nearly linear decrease of band gap energy in Si(SexS1-x)2 with increasing Se content, i.e., from SiS2 to SiSe2 which corresponds with a blue-shift in the transmission spectra from bulk SiSe2 to Si(Se0.6S0.4)2, and to SiS2. Air stability tests demonstrate the formation of toxic H2Se/H2S gas from sample oxidation at room temperature upon exposure to ambient air, and great care should be paid when handling these materials.

  7. Benthic foraminiferal stable isotope record of organic carbon fluxes during deposition of Mediterranean sapropel S1

    NASA Astrophysics Data System (ADS)

    Theodor, Marc; Schmiedl, Gerhard; Mackensen, Andreas

    2016-04-01

    We integrated Late Glacial to Holocene stable isotope records for different epi- and endobenthic foraminifera from the Mediterranean Sea in order to document the sequence of environmental changes across formation of the most recent sapropel S1. The stable carbon isotope record of epibenthic taxa corroborates results from model experiments indicating a Late Glacial onset of deep-water stagnation with short-term reventilation events during cold intervals of the Heinrich event 1, the Younger Dryas, and the 8.2 event. The stable carbon isotope difference between epi- and shallow endobenthic foraminifera exhibits marked temporal fluctuations linked to microhabitat shifts and changes in organic matter fluxes. We generated a transfer function for organic carbon fluxes based on a correlation between the stable carbon isotope signature of modern benthic foraminifera and observed organic carbon flux rates from different Mediterranean basins. Application of this transfer function to the down-core data reveals generally elevated organic matter fluxes during the Last Glacial Maximum and the Younger Dryas, while values drop significantly during the Bølling-Allerød interstadial and with onset of the Holocene. Our results support a scenario where average organic matter fluxes in the eastern Mediterranean Sea were not significantly enhanced during formation of sapropel S1. Instead, our data corroborate earlier results from benthic foraminiferal faunal successions and model experiments suggesting that sufficient amounts of organic matter are buried under oligotrophic conditions in an intermittently hypoxic water column.

  8. Isomerization, Perturbations, Calculations and the S_{1} State of C_{2}H_{2}

    NASA Astrophysics Data System (ADS)

    Baraban, J. H.; Changala, P. B.; Berk, J. R. P.; Field, R. W.; Stanton, J. F.; Merer, A. J.

    2013-06-01

    Preliminary analysis of the energy region of the cis-trans isomerization transition state on the S_{1} surface of C_{2}H_{2} has revealed novel patterns and surprising perturbations, including unusually large (and high-order) anharmonicities, as well as K-staggerings of several vibrational levels. These effects complicate the analysis considerably, and require new models and calculations to account for and predict features of the observed spectra. The ˜{A}-˜{X} spectrum of acetylene has been studied both experimentally and theoretically for almost a century, and this cycle of unexpected phenomena eliciting innovative responses is found throughout its history. Especially in the last ten years, progress in understanding the S_{1} state rovibrational level structure and cis-trans isomerization has been accelerated by combining the information available from both ab initio computation and spectroscopic observations. The resulting dialogue has then frequently suggested fruitful avenues for further experiments and calculations. Current challenges and recent results in understanding the cis-trans isomerization transition state region will be discussed in this context.

  9. Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing.

    PubMed

    Manes, Nathan P; Angermann, Bastian R; Koppenol-Raab, Marijke; An, Eunkyung; Sjoelund, Virginie H; Sun, Jing; Ishii, Masaru; Germain, Ronald N; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra

    2015-10-01

    Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P)(1) regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq was used to identify expressed target proteins, and selected reaction monitoring (SRM) mass spectrometry using internal peptide standards was used to perform absolute abundance measurements of pathway proteins. The resulting transcript and protein abundance values were strongly correlated. Measured protein abundance values, used as simulation input parameters, led to in silico pathway behavior matching in vitro measurements. Moreover, once model parameters were established, even simulated responses toward stimuli that were not used for parameterization were consistent with experimental findings. These findings demonstrate the feasibility and value of combining targeted mass spectrometry with pathway modeling for advancing biological insight.

  10. Protein crystallography beamline BL2S1 at the Aichi synchrotron

    PubMed Central

    Watanabe, Nobuhisa; Nagae, Takayuki; Yamada, Yusuke; Tomita, Ayana; Matsugaki, Naohiro; Tabuchi, Masao

    2017-01-01

    The protein crystallography beamline BL2S1, constructed at one of the 5 T superconducting bending-magnet ports of the Aichi synchrotron, is available to users associated with academic and industrial organizations. The beamline is mainly intended for use in X-ray diffraction measurements of single-crystals of macromolecules such as proteins and nucleic acids. Diffraction measurements for crystals of other materials are also possible, such as inorganic and organic compounds. BL2S1 covers the energy range 7–17 keV (1.8–0.7 Å) with an asymmetric-cut curved single-crystal monochromator [Ge(111) or Ge(220)], and a platinum-coated Si mirror is used for vertical focusing and as a higher-order cutoff filter. The beamline is equipped with a single-axis goniometer, a CCD detector, and an open-flow cryogenic sample cooler. High-pressure protein crystallography with a diamond anvil cell can also be performed using this beamline. PMID:28009576

  11. [Combination Chemotherapy Using Oxaliplatin plus S-1 for Well-Advanced Gastric Cancer].

    PubMed

    Saito, Hiroyuki; Suematsu, Yuki; Yamagishi, Shunsuke; Takahashi, Miyuki; Nakayama, Mao; Fukabori, Michiko; Morita, Akihiko; Wakabayashi, Kazuhiko; Itoh, Yutaka

    2016-11-01

    We studied the clinical efficacy of pre-operative combination chemotherapy using S-1 plus oxaliplatin for advanced gastric cancer. Four patients hadclinical Stage IV disease, 1 patient had clinical Stage III C disease, 2 patients had clinical Stage III B disease, and 1 patient had clinical Stage III A disease. The patients received 2-8 courses of oxaliplatin(130mg/m2)on day 1, andS -1 on days 1-14 every 3 weeks. The response rate was 56%(5 PR, 1 PD, and2 SD), andthe disease control rate was 88%. Toxicities were Grade 2 anemia, Grade 1 peripheral neuropathy, Grade 1 fatigue, and anorexia. Five of the 8 patients underwent R0 surgery after SOX chemotherapy, and no severe complications occurred. Histological responses were Grade 3 for 2 cases, Grade 2 for 2 cases, andGrad e 1a for 1 case. The SOX regimen showeda high objective tumor response, andis one of the promising regimens in the neoadjuvant setting for well-advanced gastric cancer.

  12. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    SciTech Connect

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. )

    1989-11-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

  13. The chiral S = -1 meson-baryon interaction with new constraints on the NLO contributions

    NASA Astrophysics Data System (ADS)

    Ramos, A.; Feijoo, A.; Magas, V. K.

    2016-10-01

    We present a study of the S = - 1 meson-baryon interaction, employing a chiral SU(3) Lagrangian up to next-to-leading order (NLO) and implementing unitarization in coupled channels. The parameters of the model have been fitted to a large set of experimental scattering data in different two-body channels, to threshold branching ratios, and to the precise SIDDHARTA value of the energy shift and width of kaonic hidrogen. In contrast to other groups, we have taken into consideration the K- p →K+Ξ- ,K0Ξ0 reaction data, since we found in a previous work to be especially sensitive to the NLO parameters of the chiral Lagrangian. In the present work we also include the Born terms, which usually have very little effect, and find them to be non-negligible in the K- p → KΞ channels, correspondingly causing significant modifications to the NLO parameters. We furthermore show that the importance of the Born terms becomes more visible in the isospin projected amplitudes of the K- p → KΞ reactions. The measurement of processes that filter single isospin components, like the KL0 p →K+Ξ0 reaction that could be measured at the proposed secondary KL0 beam at Jlab, would put valuable constraints on the chiral models describing the meson-baryon interaction in the S = - 1 sector.

  14. Optical Parameters of Spray-Deposited CdS1- y Te y Thin Films

    NASA Astrophysics Data System (ADS)

    Ikhmayies, Shadia J.

    2017-02-01

    CdS x Te1- x and CdS1- y Te y solid solutions are usually formed in the interfacial region in CdS/CdTe solar cells during the deposition of the CdTe layer and/or the processing steps of the device. In this work, indium-doped CdS1- y Te y thin films were prepared by first producing CdS:In thin films by the spray pyrolysis technique on glass substrates, then annealing the films in nitrogen atmosphere in the presence of elemental tellurium. The films were characterized by scanning electron microscopy, energy dispersive x-ray spectroscopy, and transmittance measurements. The transmittance was used to deduce the reflectance from which the optical parameters were computed. The extinction coefficient, refractive index, the real and imaginary parts of the dielectric constant, optical conductivity, and energy loss were computed, and their dependence on the composition was investigated. In addition, the dispersion of the refractive index was analyzed by the single oscillator model, and dispersion parameters were investigated.

  15. Complete genome sequence of Rhodospirillum rubrum type strain (S1T)

    SciTech Connect

    Munk, Christine; Copeland, A; Lucas, Susan; Lapidus, Alla L.; Glavina Del Rio, Tijana; Barry, Kerrie; Detter, J. Chris; Hammon, Nancy; Israni, Sanjay; Pitluck, Sam; Brettin, Thomas S; Bruce, David; Han, Cliff; Tapia, Roxanne; Gilna, Paul; Schmutz, Jeremy; Larimer, Frank W; Land, Miriam L; Kyrpides, Nikos C; Mavromatis, K; Richardson, P M; Rohde, Manfred; Goker, Markus; Klenk, Hans-Peter; Zhang, Yaoping; Roberts, Gary P.; Reslewic, Susan; Schwartz, David C.

    2011-01-01

    Rhodospirillum rubrum (Esmarch 1887) Molisch 1907 is the type species of the genus Rho- dospirillum, which is the type genus of the family Rhodospirillaceae in the class Alphaproteo- bacteria. The species is of special interest because it is an anoxygenic phototroph that pro- duces extracellular elemental sulfur (instead of oxygen) while harvesting light. It contains one of the most simple photosynthetic systems currently known, lacking light harvesting complex 2. Strain S1T can grow on carbon monoxide as sole energy source. With currently over 1,750 PubMed entries, R. rubrum is one of the most intensively studied microbial species, in partic- ular for physiological and genetic studies. Next to R. centenum strain SW, the genome se- quence of strain S1T is only the second genome of a member of the genus Rhodospirillum to be published, but the first type strain genome from the genus. The 4,352,825 bp long chro- mosome and 53,732 bp plasmid with a total of 3,850 protein-coding and 83 RNA genes were sequenced as part of the DOE Joint Genome Institute Program DOEM 2002.

  16. Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer.

    PubMed

    Suzuki, Shuji; Shimazaki, Jiro; Morishita, Keiichi; Koike, Nobusada; Harada, Nobuhiko; Hayashi, Tsuneo; Suzuki, Mamoru

    2016-10-01

    The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m(2)) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1-14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer.

  17. Electronic and vibrational structures in the S0 and S1 states of coronene

    NASA Astrophysics Data System (ADS)

    Kunishige, Sachi; Kanaoka, Ayumi; Katori, Toshiharu; Kawabata, Megumi; Baba, Masaaki; Yamanaka, Takaya; Higashibayashi, Shuhei; Sakurai, Hidehiro

    2017-01-01

    We observed the fluorescence excitation spectra and dispersed fluorescence spectra of jet-cooled coronene-h12 and coronene-d12. We analyzed the vibronic structures, assuming a planar and sixfold symmetric molecular structure (D6 h). The S1 state was identified to be 2u1B. The S12u1B ←S01g1A transition is symmetry forbidden, so the 000 band is missing in the fluorescence excitation spectrum. We found a number of vibronic bands that were assigned to the e2 g fundamental bands and their combination bands with totally symmetric a1 g vibrations. This spectral feature is similar to that of benzene although several strong e2 g bands are seen in coronene. The band shape (rotational envelope) was significantly different in each e2 g mode. It was shown that degenerate rotational levels were shifted and split by the Coriolis interaction. We calculated the Coriolis parameter using the molecular structure in the S1 state and the normal coordinate of each e2 g vibrational mode, which were obtained by theoretical calculations. The calculated band shapes well reproduced the observed ones, suggesting that the isolated coronene molecule has D6 h symmetry.

  18. Experimental signatures of spin liquid physics on the S=1/2 kagom'e lattice

    NASA Astrophysics Data System (ADS)

    Lee, Young

    2012-02-01

    I will describe our recent experimental progress on the quest to study novel ground states in frustrated magnets. New states of matter may be produced if quantum effects and frustration conspire to prevent the ground state from achieving classical order. Materials based on the kagom'e lattice appear to be ideal hosts for the possibility of a quantum spin liquid ground state in two-dimensions. I will discuss our work which includes single crystal growth, bulk characterization, and neutron scattering measurements of the S=1/2 kagom'e lattice material ZnCu3(OH)6Cl2 (also known as herbertsmithite). Recent susceptibility measurements on single crystals yield valuable information on the additional terms in the spin Hamiltonian beyond nearest neighbor Heisenberg exchange, and anomalous x-ray diffraction yields detailed information on the presence of a small amount of atomic impurities. Most interestingly, inelastic neutron scattering measurements of the spin correlations in a single crystal sample reveal a continuum of spinon excitations in this two-dimensional insulating magnet. We will discuss our results in relation to recent theories for spin liquid physics on the S=1/2 kagom'e lattice.

  19. Synthesis, characterization and thermoluminescence studies of (ZnS)1-x (MnTe)x nanophosphors.

    PubMed

    Pateria, Deepti; Baghel, R N; Bisen, D P; Jha, Piyush; Chandra, V K; Chandra, B P

    2017-05-01

    The present paper reports the thermoluminescence (TL) of (ZnS)1-x (MnTe)x nanophosphors that were prepared by a wet chemical synthesis method. The structure investigated by X-ray diffraction patterns confirms the formation of a sphalerite phase whose space group was found to be F 4¯3m. From XRD, TEM and SEM analyses the average sizes of the particles were found to be 12 nm, 11 nm and 15 nm, respectively. Initially the TL intensity increased with increasing values of x because the number of luminescence centres increased; however, for higher values of x the TL intensity decreased because of the concentration quenching. Thus the TL, mechanoluminescence and photoluminescence intensities are optimum for a particular value of x, that is for x = 0.05. Thermoluminescence of the (ZnS)1-x (MnTe)x nanophosphor has not been reported previously. There were two peaks seen in the thermoluminescence glow curves in which the first peak lay at 105-100 °C and the second peak lay at 183.5-178.5 °C. The activation energies for the first and second peaks were found to be 0.45 eV and 0.75 eV, respectively.

  20. S1 nuclease definition of highly repeated DNA sequences in the Guinea pig, Cavia porcellus.

    PubMed Central

    Hubbell, H R; Robberson, D L; Hsu, T C

    1979-01-01

    Native DNA of the Guinea pig, Cavia porcellus, purified from liver or tissue culture cells, was heat denatured and reassociated to a Cot value of 0.01 (equivalent Cot value of 7.2 x 10(-2)). The reassociated DNA was isolated by digestion with the single-strand DNA specific enzyme S1 nuclease. Spectrophotometric and radioactivity assays demonstrated that 24% of the total DNA was resistant to S1 nuclease treatment. Zero-time reassociation indicated that approximately 3% of the DNA was inverted repeat sequences. Thus, highly repeated sequences comprised 21% of the total genome. CsCl buoyant density ultracentrifugation indicated that this fraction was composed of both main band and satellite sequences. Although actinomycin D - CsCl density gradients failed to give significant separation of the repetitive sequences, distamycin A - CsCl gradients were able to fractionate the DNA into several overlapping bands. The heterogeneity of the repetitive DNA was further demonstrated by the first derivative plots calculated from their thermal denaturation profiles. This analysis revealed six major thermalytes which indicate that there may be at least six discrete components in the repetitive DNA. Images PMID:523322

  1. Yielding of tantalum at strain rates up to 109 s-1

    NASA Astrophysics Data System (ADS)

    Crowhurst, Jonathan C.; Armstrong, Michael R.; Gates, Sean D.; Zaug, Joseph M.; Radousky, Harry B.; Teslich, Nick E.

    2016-08-01

    We have used a 45 μJ laser pulse to accelerate the free surface of fine-grained tantalum films up to peak velocities of ˜1.2 km s-1. The films had thicknesses of ˜1-2 μm and in-plane grain widths of ˜75-150 nm. Using ultrafast interferometry, we have measured the time history of the velocity of the surface at different spatial positions across the accelerated region. The initial part of the histories (assumed to correspond to the "elastic precursor" observed previously) exhibited measured strain rates of ˜0.6 to ˜3.2 × 109 s-1 and stresses of ˜4 to ˜22 GPa. Importantly, we find that elastic amplitudes exhibit little variation with strain rate for a constant peak surface velocity, even though, via covariation of the strain rate with peak surface velocity, they vary with strain rate. Furthermore, by comparison with data obtained at lower strain rates, we find that amplitudes are much better predicted by peak velocities rather than by either strain rate or sample thickness.

  2. Epidermal surface antigen (MS17S1) is highly conserved between mouse and human

    SciTech Connect

    Cho, Y.J.; Chema, D.; Cho, M.

    1995-05-20

    A mouse monoclonal antibody ECS-1 raised to human keratinocytes detects a 35-kDa epidermal surface antigen (ESA) and causes keratinocyte dissociation in vitro. ECS-1 stains skin of 16-day mouse embryo and 8- to 9-week human fetus. Mouse Esa cDNA encodes a 379-amino-acid protein that is 99.2% identical to the human, differing at only 3 amino acids. The gene (M17S1) was mapped to mouse chromosome 11, highlighting the conserved linkage synteny existing between human chromosome 17 and mouse chromosome 11. Although the nude locus has been mapped to the same region of chromosome 11, no abnormalities in protein, mRNA, or cDNA or genomic sequences were detected in nude mice. However, both nude and control mice were found to have a second Esa mRNA transcript that conserves amino acid sequence and molecular weight. The mouse and human 5{prime} and 3{prime} untranslated sequences are conserved. Similar RNA folding patterns of the 5{prime} untranslated region are predicted despite a 91-bp insertion in the mouse. These data suggest that both the function and the regulation of ESA protein are of importance and that Esa (M17S1) is not the nude locus gene. 42 refs., 7 figs., 3 tabs.

  3. Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing*

    PubMed Central

    Manes, Nathan P.; Angermann, Bastian R.; Koppenol-Raab, Marijke; An, Eunkyung; Sjoelund, Virginie H.; Sun, Jing; Ishii, Masaru; Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra

    2015-01-01

    Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P)1 regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq was used to identify expressed target proteins, and selected reaction monitoring (SRM) mass spectrometry using internal peptide standards was used to perform absolute abundance measurements of pathway proteins. The resulting transcript and protein abundance values were strongly correlated. Measured protein abundance values, used as simulation input parameters, led to in silico pathway behavior matching in vitro measurements. Moreover, once model parameters were established, even simulated responses toward stimuli that were not used for parameterization were consistent with experimental findings. These findings demonstrate the feasibility and value of combining targeted mass spectrometry with pathway modeling for advancing biological insight. PMID:26199343

  4. Low-energy spin dynamics of the s = 1/2 kagome system herbertsmithite.

    PubMed

    Nilsen, G J; de Vries, M A; Stewart, J R; Harrison, A; Rønnow, H M

    2013-03-13

    The low-energy (ε = ħω < 1 meV), low-temperature (T = 0.05 K) spin dynamics of the s = 1/2 kagome candidate herbertsmithite are probed in the presence of magnetic fields up to 2.5 T. The zero-field spectra reveal a very weak continuum of scattering at T = 10 K and a broad inelastic peak centred at ε(max) = 0.2 meV at lower temperatures, T < 1 K. The broad peak is found to be strongly damped, with a liquid-like structure factor implying correlations at length scales up to r = 6 Å. The field dependence of the peak appears to follow the Zeeman splitting of s = 1/2 excitations, consistent with the weakly split 'doublets' observed in low-temperature specific heat. A possible explanation of these observations is a short-range correlated state involving defect spins between the kagome planes and moments in the kagome layers.

  5. Dynamics of S 1 acetone studied with single rotorvibronic level resolution

    NASA Astrophysics Data System (ADS)

    Bitto, H.

    1994-08-01

    The spectroscopy and dynamics of selected vibronic bands of the S 1(nπ *) ← S 0 transition of acetone and acetone- d6 were studied with single rotational-torsional-vibronic (rotorvibronic) level resolution in a jet up to an S 1 excess energy of 1300 cm -1. Using clean coherent excitation with Fourier transform-limited nanosecond laser pulses quantum beats were observed in the time-resolved fluorescence and were attributed to coherently excited siglet-triplet eigenstates as identified by their magnetic properties. In the 8 123 0- and the 8 1 23 0+I(2,1) state of acetone, and the 7 1I(1,0) state of aceton- d6, lifetimes increase with the rotational quantum number of the excited state N due to a breakdown of K selection rules for the spin-orbit interaction in this very asymmetric rotor. In the 8 123 0- state, the rotorvibronic levels of the methyl torsion tunnelling component with G symmetry exhibit the longest lifetimes among the tunnelling components. Vibrational coupling of G torsional levels in the triplet manifold favoured by symmetry is proposed to selectively increase the density of coupling triplet states and, hence, the lifetime of the eigenstates.

  6. Transcatheter arterial chemoembolisation (TACE) plus S-1 for the treatment of BCLC stage B hepatocellular carcinoma refractory to TACE

    PubMed Central

    Huang, Wu-Kui; Yang, Shu-Fa; You, Li-na; Liu, Mo; Liu, Deng-Yao; Gu, Peng

    2017-01-01

    Aim of the study To assess the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus S-1 for the treatment of Barcelona Clinic Liver Cancer (BCLC) Stage B HCC refractory to TACE. Material and methods 26 patients meeting the eligibility criteria were enrolled. TACE was given on day 1, and S-1 on days 2–15. Tumor assessment was performed one month later according to mRECIST. The primary endpoints were TTP and OS. Results Twenty-six patients received 176 TACE interventions in all. Fifteen patients of TACE plus S-1 received a total of 55 cycles of treatment of S-1, with a median of 4 cycles (range, 2–6). The total dose of S-1 was 6165 mg per day, while average was 120 mg (range, 100–125 mg) for 15 patients of TACE plus S-1. Median TTP and OS of TACE plus S-1 were 6 months (95% CI: 4.7–7.3) and 18 months (95% CI: 15.3–24.7), respectively, while TACE monotherapy was 4 months (95% CI: 2.4–5.6) and 13 months (95% CI: 9.8–16.2), respectively, and significant differences were detected. Though there were higher DCRs in patients of TACE plus S-1, no significant differences were detected. A total of 612 adverse events occurred during the course of the treatment, 367 in TACE plus S-1 and 245 in TACE mono-therapy. There were significant differences to anorexia and nausea, but they were tolerable. Conclusions TACE plus S-1 in the present analysis was tolerable and associated with an interesting TTP and OS. TACE plus S-1 may be used as a new treatment method to BCLC Stage B HCC refractory to TACE. PMID:28239285

  7. Far-UV observations of comet C/2012 S1 (ISON) with FORTIS

    NASA Astrophysics Data System (ADS)

    McCandliss, Stephan R.; Feldman, Paul D.; Weaver, Harold A.; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, Samuel H.

    2015-01-01

    Far-UV imagery and objective grating spectroscopy of comet C/2012 S1 (ISON) were acquired from NASA sounding rocket 36.296 UG, launched on 20 November 2013 at 04:40 MST (20.48 Nov 2013 UT), 8.32 days pre-perihelion, from the White Sands Missile Range, NM. The comet was 0.1° below ground horizon, 0.44 AU from the Sun, 0.86 AU from the Earth, and at a solar elongation of 26.3°. The payload reached an apogee of 279 km and the total time pointed at the comet was 353 s. At the time of launch ISON was undergoing a factor of 5 increase in water production rate, going from 3.5e29 to 19.6e29 molecules s-1between 19.6 and 21.6 Nov (Combi et al. 2014), marking what is thought to be a final fragmentation event (Sekanina & Kracht 2014). Our instrument, a wide-field multi-object spectro-telescope called FORTIS (Far-UV Off Rowland-circle Telescope for Imaging and Spectroscopy), observed Lyα emissions in an objective grating mode through an open microshutter array, developed at the Goddard Space Flight Center, over a (1/2°)2 field-of-view. After accounting for slit losses and deadtime corrections we find a preliminary lower limit to the Lyα surface brightness of ~ 400 kilorayleighs, yielding a hydrogen production rate of QH ~ 5e29 atoms s-1, in reasonable agreement with the Combi result. We also acquired a broadband image of the comet in the 1280 to 1900 Å bandpass. This image shows a drop in count rate proportional to altitude caused by increased absorption of cometary emissions by terrestrial O2 located in the lower thermosphere. O2 absorption acts as a selective time dependent filter that attenuates cometary emissions from different atomic and molecular species at different rates during descent. Preliminary analysis suggests that the dominant species in a (1e5 km)2 nuclear region is neutral carbon. The radial profile in comparison to a Haser model suggests that the C parent molecule had a lifetime (at 1 AU) ~ 105 s; much shorter than the expected lifetime of CO. We

  8. The excitonic photoluminescence mechanism and lasing action in band-gap-tunable CdS1-xSex nanostructures

    NASA Astrophysics Data System (ADS)

    Dai, Jun; Zhou, Pengxia; Lu, Junfeng; Zheng, Hongge; Guo, Jiyuan; Wang, Fang; Gu, Ning; Xu, Chunxiang

    2015-12-01

    Bandgap tunable semiconductor materials have wide application in integrated-optoelectronic and communication devices. The CdS1-xSex ternary semiconductor materials covering green-red bands have been reported previously, but their basic band-gap and optical properties crucial to the performance of the CdS1-xSex-based optoelectronic devices have not been deeply understood. In this paper, we theoretically simulated and discussed the feasibility of bandgap-tunable CdS1-xSex nanomaterials for designing wavelength tunable microlasers. Then we fabricated the CdS1-xSex nanobelts with their band gap ranging from 2.4 to 1.74 eV by adjusting the composition ratio x in the vapor-phase-transport growth process. The temperature-dependent photoluminescence and exciton-related optical constants of the CdS1-xSex nanobelts were carefully demonstrated. Finally, the wavelength-tunable Fabry-Perot lasing in CdS1-xSex nanobelts was obtained, and the Fabry-Perot lasing mechanism was numerically simulated by the FDTD method. The systematic results on the mechanism of the tunable band gap, exciton properties and lasing of the CdS1-xSex nanostructure help us deeply understand the intrinsic optical properties of this material, and will build a strong foundation for future application of green-red wavelength-tunable CdS1-xSex microlasers.

  9. Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P).

    PubMed

    Zhang, Lin; Urtz, Nicole; Gaertner, Florian; Legate, Kyle R; Petzold, Tobias; Lorenz, Michael; Mazharian, Alexandra; Watson, Steve P; Massberg, Steffen

    2013-08-01

    Human megakaryocytes (MKs) release trillions of platelets each day into the circulation to maintain normal homeostatic platelet levels. We have previously shown that extracellular sphingosine 1-phosphate (S1P) plays a key role in thrombopoiesis via its receptor S1pr1. In addition to its role as an extracellular mediator, S1P can also function as a second messenger in the intracellular compartment. Although signaling via intracellular S1P is involved in various cellular processes, a role in thrombopoiesis has not been examined. Sphingosine kinases are the key enzymes that produce intracellular S1P. Here we report that sphingosine kinase 2 (Sphk2) is the major messenger RNA species present in MKs. Sphk2 predominantly localizes to the nucleus and is the major source of intracellular S1P in MKs. Loss of Sphk2 significantly reduced intracellular S1P in MKs and downregulated the expression and activity of Src family kinases (SFKs). Loss of Sphk2 and inhibition of SFK activity resulted in defective intravascular proplatelet shedding, the final stage of thrombopoiesis. Correspondingly, mice lacking Sphk2 in the hematopoietic system display thrombocytopenia. Together, our data suggest that Sphk2 provides the source of intracellular S1P that controls thrombopoiesis, which is associated with SFK expression and activity in MKs.

  10. 75 FR 27411 - Airworthiness Directives; Turbomeca Arriel 1B, 1D, 1D1, and 1S1 Turboshaft Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    ... (that incorporate Turbomeca Modification (mod) TU 148), Arriel 1D, 1D1, and 1S1 turboshaft engines that do not incorporate mod TU 347. That AD also requires initial and repetitive replacements of 2nd stage... incorporate mod TU 148), 1D, 1D1, and 1S1 turboshaft engines that do not incorporate mod TU 347. We...

  11. Complete Genome Sequence of a Marine Bacterium, Pseudomonas pseudoalcaligenes Strain S1, with High Mercury Resistance and Bioaccumulation Capacity

    PubMed Central

    Liu, Bing; Bian, Chao; Huang, Huiwei; Yin, Zhiwei

    2016-01-01

    Pseudomonas pseudoalcaligenes S1, a marine bacterium, exhibited strong resistance to a high concentration of Hg2+ and remarkable Hg2+ bioaccumulation capacity. Here, we report the 6.9-Mb genome sequence of P. pseudoalcaligenes S1, which may help clarify its phylogenetic status and provide further understanding of the mechanisms of mercury bioremediation in a marine environment. PMID:27198018

  12. The Occurrence of Type S1A Serine Proteases in Sponge and Jellyfish

    NASA Technical Reports Server (NTRS)

    Rojas, Ana; Doolittle, Russell F.

    2003-01-01

    Although serine proteases are found in all kinds of cellular organisms and many viruses, the classic "chymotrypsin family" (Group S1A by th e 1998 Barrett nomenclature) has an unusual phylogenetic distribution , being especially common in animals, entirely absent from plants and protists, and rare among fungi. The distribution in Bacteria is larg ely restricted to the genus Streptomyces, although a few isolated occ urrences in other bacteria have been reported. The family may be enti rely absent from Archaea. Although more than a thousand sequences have been reported for enzymes of this type from animals, none of them ha ve been from early diverging phyla like Porifera or Cnidaria, We now report the existence of Group SlA serine proteases in a sponge (phylu m Porifera) and a jellyfish (phylum Cnidaria), making it safe to conc lude that all animal groups possess these enzymes.

  13. Optical and Phonon Characterization of Ternary CdSe x S1- x Alloy Quantum Dots

    NASA Astrophysics Data System (ADS)

    Thi, L. A.; Cong, N. D.; Dang, N. T.; Nghia, N. X.; Quang, V. X.

    2016-05-01

    Ternary CdSe x S1- x alloy quantum dots (QDs) were synthesized using a wet chemical method. Their morphology, particle size, structural, optical, and vibrational properties were investigated using transmission electron microscopy, x-ray diffraction, UV-Vis, fluorescence and Raman spectroscopy, respectively. The optical and vibrational properties of the QDs can be controlled by adjusting the Se/S molar ratio. The absorption and emission peaks shift to a longer wavelength range when increasing the Se content. The presence of two CdSe-like and CdS-like longitudinal optical phonon modes was observed. The dependencies of the optical and phonon modes on the Se content are discussed in detail.

  14. Mott lobes of the S =1 Bose-Hubbard model with three-body interactions

    NASA Astrophysics Data System (ADS)

    Hincapie-F, A. F.; Franco, R.; Silva-Valencia, J.

    2016-09-01

    Using the density-matrix renormalization-group method, we studied the ground state of the one-dimensional S =1 Bose-Hubbard model with local three-body interactions, which can be a superfluid or a Mott insulator state. We drew the phase diagram of this model for both ferromagnetic and antiferromagnetic interaction. Regardless of the sign of the spin-dependent coupling, we obtained that the Mott lobes area decreases as the spin-dependent strength increases, which means that the even-odd asymmetry of the two-body antiferromagnetic chain is absent for local three-body interactions. For antiferromagnetic coupling, we found that the density drives first-order superfluid-Mott insulator transitions for even and odd lobes. Ferromagnetic Mott insulator and superfluid states were obtained with a ferromagnetic coupling, and a tendency to a "long-range" order was observed.

  15. O/S-1/ interactions - The product channels. [collisional electron quenching and chemical reaction pathway frequencies

    NASA Technical Reports Server (NTRS)

    Slanger, T. G.; Black, G.

    1978-01-01

    The first measurements are reported of the reaction pathways for the interaction between oxygen atoms in the 4.19 eV S-1 state, and four molecules, N2O, CO2, H2O, and NO. Distinction is made between three possible paths - quenching to O(D-1), quenching to O(P-3), and chemical reaction. With N2O, the most reasonable interpretation of the data indicates that there no reaction, in sharp contrast with the interaction between O(D-1) and N2O, which proceeds entirely by reaction. Similarly, there is no reaction with CO2. With H2O, the reactive pathway is the dominant one, although electronic quenching is not negligible. With NO, O(D-1) is the preferred product.

  16. The Case for a Hubble Constant of 30 km s-1 Mpc-1.

    PubMed

    Bartlett, J G; Blanchard, A; Silk, J; Turner, M S

    1995-02-17

    Although recent determinations of the distance to the Virgo cluster based on Cepheid variable stars represent an important step in pinning down the Hubble constant, after 65 years a definitive determination of the Hubble constant still eludes cosmologists. At present, most of the observational determinations place the Hubble constant between 40 and 90 kilometers per second per megaparsec (km s(-1) Mpc(-1)). The case is made here for a Hubble constant that is even smaller than the lower bound of the accepted range on the basis of the great advantages, all theoretical in nature, of a Hubble constant of around 30 kilometers per second per megaparsec. Such a value for the Hubble cures all of the ills of the current theoretical orthodoxy, that is, a spatially flat universe composed predominantly of cold dark matter.

  17. Ferrimagnetic states in S = 1/2 frustrated Heisenberg chains with period 3 exchange modulation

    NASA Astrophysics Data System (ADS)

    Hida, K.

    2007-04-01

    The ground state properties of the S = 1/2 frustrated Heisenberg chain with period 3 exchange modulation are investigated using the numerical diagonalization and density matrix renormalization group (DMRG) method. It is known that this model has a magnetization plateau at one third of the saturation magnetization Ms. On the other hand, the ground state is ferrimagnetic even in the absence of frustration if one of the nearest neighbour bond is ferromagnetic and the others are antiferromagnetic. In the present work, we show that this ferrimagnetic state continues to the region in which all bonds are antiferromagnetic if the frustration is strong. This state further continues to the above-mentioned 1/3 plateau state. In between, we also find the noncollinear ferrimagnetic phase in which the spontaneous magnetization is finite but less than Ms/3. The intuitive interpretation for the phase diagram is given and the physical properties of these phases are discussed.

  18. Therapeutic Strategies and Pharmacological Tools Influencing S1P Signaling and Metabolism.

    PubMed

    Vogt, Dominik; Stark, Holger

    2017-01-01

    During the last two decades the study of the sphingolipid anabolic, catabolic, and signaling pathways has attracted enormous interest. Especially the introduction of fingolimod into market as first p.o. therapeutic for the treatment of multiple sclerosis has boosted this effect. Although the complex regulation of sphingosine-1-phosphate (S1P) and other catabolic and anabolic sphingosine-related compounds is not fully understood, the influence on different (patho)physiological states from inflammation to cytotoxicity as well as the availability of versatile pharmacological tools that represent new approaches to study these states are described. Here, we have summarized various aspects concerning the many faces of sphingolipid function modulation by different pharmacological tools up to clinical candidates. Due to the immense heterogeneity of physiological or pharmacological actions and complex cross regulations, it is difficult to predict their role in upcoming therapeutic approaches. Currently, inflammatory, immunological, and/or antitumor aspects are discussed.

  19. Technical evaluation report for the demonstration of radio frequency soil decontamination at Site S-1

    SciTech Connect

    Lyon, C.R.; Blanchard, C.F.; Whitt, L.H.

    1995-04-01

    The Air Force`s Armstrong Laboratory at Tyndall Air Force Base, Florida, has supported the research and development of Radio Frequency Soil Decontamination. Radio frequency soil decontamination is essentially a heat-assisted soil vapor extraction process. Site S-1 at Kelly Air Force Base, San Antonio, Texas, was selected for the demonstration of two patented techniques. The site is a former sump that collected spills and surface run-off from a waste petroleum, oils, and lubricants and solvent storage and transfer area. In 1993, a technique developed by the IIT Research Institute using an array of electrodes placed in the soil was demonstrated. In 1994, a technique developed by KAI Technologies, Inc. using a single applicator placed in a vertical borehole was demonstrated. Approximately 120 tons of soil were heated during each demonstration to a temperature of about 150 degrees Celsius.

  20. Lower Extremity Radicular Pain Caused by Entrapped Sigmoid Colon Between L5 and S1 Vertebrae

    PubMed Central

    Ko, Sanghyung; Park, Noh Kyoung; Cho, Kyoung Jin; Baek, Jung Hyun; Lim, Jeong-Wook; Choi, Dongjin

    2015-01-01

    Intestinal entrapment between two vertebral bodies is very rare. In all previous cases, it occurred by major trauma. However, the bowel entrapment between two vertebral bodies without trauma has never been reported, not to mention as the cause of lower extremity radicular pain. We describe the case of an 82-year-old female patient with right lower extremity radicular pain without recent trauma history. The patient was diagnosed sigmoid colon entrapment between the L5 and S1 vertebrae by lumbar spinal computerized tomography and magnetic resonance imaging, and showed improvement in radicular pain after manual reduction of interpositioned colon during surgery. Intestinal entrapment between two vertebrae without trauma is caused by degenerative and vacuum changes of the intervertebral disc combined with the anterior longitudinal ligament injury. PMID:26619145

  1. Semiclassical on-the-fly computation of the S(0)-->S(1) absorption spectrum of formaldehyde.

    PubMed

    Tatchen, Jörg; Pollak, Eli

    2009-01-28

    The anharmonic S(0)-->S(1) vibronic absorption spectrum of the formaldehyde molecule is computed on the fly using semiclassical dynamics. This first example of an on-the-fly semiclassical computation of a vibronic spectrum was achieved using a unit prefactor modified frozen Gaussian semiclassical propagator for the excited state. A sample of 6000 trajectories sufficed for obtaining a converged spectrum, which is in reasonable agreement with experiment. Similar agreement is not obtained when using a harmonic approximation for the spectrum, demonstrating the need for a full anharmonic computation. This first example provides a resolution of approximately 100 cm(-1). Potential ways of improving the methodology and obtaining higher resolution and accuracy are discussed.

  2. Picosecond transient gratings in CdS1- xSex mixed crystals

    NASA Astrophysics Data System (ADS)

    Dörnfeld, C.; Noll, G.; Schwab, H.; Hvam, J. M.; Weber, Ch.; Renner, R.; Göbel, E. O.; Reznitsky, A.; Lyssenko, V.; Pendjur, S. A.; Talensky, O. N.; Klingshirn, C.

    1990-04-01

    We performed transient grating experiments to study various relaxation processes of localized excitons in CdS1 xSex mixed crystals. At low temperatures we observe a strong nonlinear response, spectrally in the localized states. We measured the phase relaxation time of localized excitons with a correlation technique. At low excitation levels we found long phase relaxation times of 75 ps. In a three beam configuration of a transient grating experiment we investigated the recombination as well as the diffusion of excitons within the localized states. We observed a reduced mobility compared to the mobility of free excitons in the pure compounds and found diffusion coefficients D < 2 cm2/ s.

  3. Linear and nonlinear optical studies of CdS1- x Se x quantum dots

    NASA Astrophysics Data System (ADS)

    Uhrig, A.; Banyai, L.; Gaponenko, S.; Wörner, A.; Neuroth, N.; Klingshirn, C.

    1991-03-01

    In this contribution we present and discuss our measurements on CdS1- x Se x quantum dots in a glass matrix. In linear absorption measurements we find the typical blue shift of the transitions with decreasing crystallite radius due to quantization. The luminescence shows a significant Stokes shift with respect to absorption, which is interpreted in terms of strong exciton-phonon coupling and allows to deduce the Huang-Rhys factor S. Under high excitation we find an additional emission band on the high energy side, which can be attributed to the recombination of an excited two electron-hole pair state to a one electron-hole pair state in agreement with theory. Pump and probe beam experiments give a bleaching but no hole burning. Finally we discuss some open questions especially concerning the high energy structures in the absorption spectrum.

  4. Supersymmetry and CP violation in {delta}S=1 {tau} decays

    SciTech Connect

    Delepine, D.; Faisel, G.; Khalil, S.; Lopez Castro, G.

    2006-09-01

    We compute the supersymmetry (SUSY) effective Hamiltonian that describes the {delta}S=1 semileptonic decays of tau leptons. We provide analytical expressions for supersymmetric contribution to {tau}{yields}us{nu}{sub {tau}} transition in mass insertion approximation. We show that SUSY contributions may enhance the CP asymmetry of {tau}{yields}K{pi}{nu}{sub {tau}} decays by several orders of magnitude with respect to the standard model expectations. However, the resulting asymmetry is still well below the current experimental limits obtained by CLEO Collaborations. We emphasize that measuring CP rate asymmetry in this decay larger than 10{sup -6} would be a clear evidence of physics beyond the supersymmetric extensions of the standard model.

  5. Tarlov cyst as a rare cause of S1 radiculopathy: A case report.

    PubMed

    Nadler, S F; Bartoli, L M; Stitik, T P; Chen, B

    2001-05-01

    A 37-year-old female physician presented with a chief complaint of left posterior thigh pain, which began insidiously approximately 4 months before her initial examination. Initially, she had been evaluated by her physician, and magnetic resonance imaging (MRI) was ordered. The MRI scan was reported to be within normal limits, with the exception of minimal disc bulging at L4-5. She had received physical therapy with little benefit and was referred for physiatric assessment. Review of the patient's original MRI scan showed the presence of perineurial (Tarlov) cysts within the sacral canal at the level of S2, with compression of the adjacent nerve root. Subsequent electrodiagnostic testing showed axonal degeneration consistent with an S1 radiculopathy. Tarlov cysts can be a rare cause of lumbosacral radiculopathy and should be considered in the differential diagnosis of radicular leg pain.

  6. Classifying magnetic and superfluid equilibrium states in magnets with the spin s = 1

    NASA Astrophysics Data System (ADS)

    Kovalevskii, M. Yu.

    2016-03-01

    Based on the method of quasiaverages, we classify magnetic and superfluid equilibrium states in magnets with the spin s = 1. Under certain simplifications, assumptions about the residual symmetry of degenerate states and the transformation properties of order parameter operators under transformations generated by additive integrals of motions lead to linear algebraic equations for a classification of the equilibrium means of the order parameters. We consider different cases of the magnetic SO(3) or SU(3) symmetry breaking and obtain solutions for the vector and tensor order parameters for particular forms of the parameters of the residual symmetry generators. We study the equilibriums of magnets with simultaneously broken phase and magnetic symmetries. We find solutions of the classification equations for superfluid equilibrium states and establish relations between the parameters of the residual symmetry generator that allow the thermodynamic coexistence of nonzero equilibrium means of the order parameters.

  7. Critical Keller-Segel meets Burgers on {{{S}}^{1}} : large-time smooth solutions

    NASA Astrophysics Data System (ADS)

    Burczak, Jan; Granero-Belinchón, Rafael

    2016-12-01

    We show that solutions to the parabolic-elliptic Keller-Segel system on {{{S}}1} with critical fractional diffusion (- Δ ){{}\\frac{1{2}}} remain smooth for any initial data and any positive time. This disproves, at least in the periodic setting, the large-data-blowup conjecture by Bournaveas and Calvez [15]. As a tool, we show smoothness of solutions to a modified critical Burgers equation via a generalization of the ingenious method of moduli of continuity by Kiselev, Nazarov and Shterenberg [35] over a setting where the considered equation has no scaling. This auxiliary result may be interesting by itself. Finally, we study the asymptotic behavior of global solutions corresponding to small initial data, improving the existing results.

  8. IMAGING COMET ISON C/2012 S1 IN THE INNER CORONA AT PERIHELION

    SciTech Connect

    Druckmüller, Miloslav; Habbal, Shadia Rifai; Aniol, Peter; Ding, Adalbert; Morgan, Huw

    2014-04-01

    Much anticipation and speculation were building around comet ISON, or C/2012 S1, discovered on 2012 September 21 by the International Scientific Optical Network telescope in Russia, and bound for the Sun on 2013 November 28, with a closest heliocentric approach distance of 2.7 R {sub ☉}. Here we present the first white light image of the comet's trail through the inner corona. The image was taken with a wide field Lyot-type coronagraph from the Mees Observatory on Haleakala at 19:12 UT, past its perihelion passage at 18:45 UT. The perfect match between the comet's trail captured in the inner corona and the trail that had persisted across the field of view of 2-6 R {sub ☉} of the Solar and Heliospheric Observatory Large Angle and Spectrometric Coronagraph Experiment/C2 coronagraph at 19:12 UT demonstrates that the comet survived its perihelion passage.

  9. Early changes in shoot transcriptome of rice in response to Rhodotorula mucilaginosa JGTA-S1

    PubMed Central

    Saha, Chinmay; Seal, Anindita

    2015-01-01

    Yeasts of Rhodotorula genus have been reported to show endophytic colonization in different plants. Some of the Rhodotorula species are found to exhibit plant growth promoting activities and also have been reported to protect plants against invading pathogens. A yeast strain closely related to Rhodotorula mucilaginosa was isolated from the endosphere of Typha angustifolia collected from a Uranium mine. A microarray analysis was performed to investigate the early changes in rice shoot transcripts in response to this yeast (R. mucilaginosa JGTA-S1). Transcriptional changes were monitored in 6 h and 24 h treated rice plant shoots as compared to 0 h control. The microarray data has been submitted to the NCBI GEO repository under the accession number of GSE64321. PMID:26697384

  10. Memo has a novel role in S1P signaling and is [corrected] crucial for vascular development.

    PubMed

    Kondo, Shunya; Bottos, Alessia; Allegood, Jeremy C; Masson, Regis; Maurer, Francisca G; Genoud, Christel; Kaeser, Patrick; Huwiler, Andrea; Murakami, Masato; Spiegel, Sarah; Hynes, Nancy E

    2014-01-01

    Memo is a conserved protein that was identified as an essential mediator of tumor cell motility induced by receptor tyrosine kinase activation. Here we show that Memo null mouse embryonic fibroblasts (MEFs) are impaired in PDGF-induced migration and this is due to a defect in sphingosine-1-phosphate (S1P) signaling. S1P is a bioactive phospholipid produced in response to multiple stimuli, which regulates many cellular processes. S1P is secreted to the extracellular milieu where it exerts its function by binding a family of G-protein coupled receptors (S1PRs), causing their activation in an autocrine or paracrine manner. The process, termed cell-autonomous S1PR signaling, plays a role in survival and migration. Indeed, PDGF uses cell-autonomous S1PR signaling to promote cell migration; we show here that this S1P pathway requires Memo. Using vascular endothelial cells (HUVECs) with Memo knock-down we show that their survival in conditions of serum-starvation is impaired. Furthermore, Memo loss in HUVECs causes a reduction of junctional VE-cadherin and an increase in sprout formation. Each of these phenotypes is rescued by S1P or S1P agonist addition, showing that Memo also plays an important role in cell-autonomous S1PR signaling in endothelial cells. We also produced conventional and endothelial cell-specific conditional Memo knock-out mouse strains and show that Memo is essential for embryonic development. Starting at E13.5 embryos of both strains display bleeding and other vascular problems, some of the phenotypes that have been described in mouse strains lacking S1PRs. The essential role of Memo in embryonic vascular development may be due in part to alterations in S1P signaling. Taken together our results show that Memo has a novel role in the S1P pathway and that Memo is needed to promote cell-autonomous S1PR activation.

  11. S1 Pocket of a Bacterially Derived Subtilisin-like Protease Underpins Effective Tissue Destruction*

    PubMed Central

    Wong, Wilson; Wijeyewickrema, Lakshmi C.; Kennan, Ruth M.; Reeve, Shane B.; Steer, David L.; Reboul, Cyril; Smith, A. Ian; Pike, Robert N.; Rood, Julian I.; Whisstock, James C.; Porter, Corrine J.

    2011-01-01

    The ovine footrot pathogen, Dichelobacter nodosus, secretes three subtilisin-like proteases that play an important role in the pathogenesis of footrot through their ability to mediate tissue destruction. Virulent and benign strains of D. nodosus secrete the basic proteases BprV and BprB, respectively, with the catalytic domain of these enzymes having 96% sequence identity. At present, it is not known how sequence variation between these two putative virulence factors influences their respective biological activity. We have determined the high resolution crystal structures of BprV and BprB. These data reveal that that the S1 pocket of BprV is more hydrophobic but smaller than that of BprB. We show that BprV is more effective than BprB in degrading extracellular matrix components of the host tissue. Mutation of two residues around the S1 pocket of BprB to the equivalent residues in BprV dramatically enhanced its proteolytic activity against elastin substrates. Application of a novel approach for profiling substrate specificity, the Rapid Endopeptidase Profiling Library (REPLi) method, revealed that both enzymes prefer cleaving after hydrophobic residues (and in particular P1 leucine) but that BprV has more restricted primary substrate specificity than BprB. Furthermore, for P1 Leu-containing substrates we found that BprV is a significantly more efficient enzyme than BprB. Collectively, these data illuminate how subtle changes in D. nodosus proteases may significantly influence tissue destruction as part of the ovine footrot pathogenesis process. PMID:21990366

  12. Role of S'1 loop residues in the substrate specificities of pepsin A and chymosin.

    PubMed

    Kageyama, Takashi

    2004-12-07

    Proteolytic specificities of human pepsin A and monkey chymosin were investigated with a variety of oligopeptides as substrates. Human pepsin A had a strict preference for hydrophobic/aromatic residues at P'1, while monkey chymosin showed a diversified preferences accommodating charged residues as well as hydrophobic/aromatic ones. A comparison of residues forming the S'1 subsite between mammalian pepsins A and chymosins demonstrated the presence of conservative residues including Tyr(189), Ile(213), and Ile(300) and group-specific residues in the 289-299 loop region near the C terminus. The group-specific residues consisted of hydrophobic residues in pepsin A (Met(289), Leu/Ile/Val(291), and Leu(298)) and charged or polar residues in chymosins (Asp/Glu(289) and Gln/His/Lys(298)). Because the residues in the loop appeared to be involved in the unique specificities of respective types of enzymes, site-directed mutagenesis was undertaken to replace pepsin-A-specific residues by chymosin-specific ones and vice versa. A yeast expression vector for glutathione-S-transferase fusion protein was newly developed for expression of mutant proteins. The specificities of pepsin-A mutants could be successfully altered to the chymosin-like preference and those of chymosin mutants, to pepsin-like specificities, confirming residues in the S'1 loop to be essential for unique proteolytic properties of the enzymes. An increase in preference for charged residues at P'1 in pepsin-A mutants might have been due to an increase in the hydrogen-bonding interactions. In chymosin mutants, the reverse is possible. The changes in the catalytic efficiency for peptides having charged residues at P'1 were dominated by k(cat) rather than K(m) values.

  13. Conformational dynamics of threonine 195 and the S1 subsite in functional trypsin variants.

    PubMed

    Gokey, Trevor; Baird, Teaster T; Guliaev, Anton B

    2012-11-01

    Replacing the catalytic serine in trypsin with threonine (S195T variant) leads to a nearly complete loss of catalytic activity, which can be partially restored by eliminating the C42-C58 disulfide bond. The 0.69 μs of combined explicit solvent molecular dynamics (MD) simulations revealed continuous rearrangement of T195 with different conformational preferences between five trypsin variants tested. Among three conformational families observed for the T195 residue, one showed the T195 hydroxyl in a conformation analogous to that of the serine residue in wild-type trypsin, positioning the hydroxyl oxygen atom for attack on the carbonyl carbon of the peptide substrate. MD simulations demonstrated that this conformation was more populated for the C42A/C58V/S195T and C42A/C58A/S195T triple variants than for the catalytically inactive S195T variant and correlated with restored enzymatic activities for triple variants. In addition, observation of the increased motion of the S214-G219 segment in the S195T substituted variants suggested an existence of open and closed conformations for the substrate binding pocket. The closed conformation precludes access to the S1 binding site and could further reduce enzymatic activities for triple variants. Double variants with intact serine residues (C42A/C58A/S195 and C42A/C58V/S195) also showed interchange between closed and open conformations for the S214-G219 segment, but to a lesser extent than the triple variants. The increased conformational flexibility of the S1 subsite, which was not observed for the wild-type, correlated with reduced enzymatic activities and suggested a possible mode of substrate regulation for the trypsin variants tested.

  14. [Response in a case of inoperable bile duct cancer treated by combined chemotherapy of S-1 and gemcitabine].

    PubMed

    Akiyama, Nobuhiro; Ayata, Sakura; Maruyama, Yuzuru; Tsukada, Yoshihisa

    2010-08-01

    A 60-year-old male patient was diagnosed as bile duct cancer with left neck and abdominal para-aortic lymph node metastasis. He was treated by combined chemotherapy of S-1 and gemcitabine(GEM). S-1 (120 mg/day) was administered 14 days followed by 14 days rest as one course. GEM (1,000 mg/m2) was administered at 8 and 15 days after the start of S-1. Combined therapy could be continued, though S-1 and GEM were reduced for neutropemia. After 5 courses of treatment, CT and MRCP revealed a partial response. S-1/GEM combined therapy was effective for inoperable biliary tract carcinoma.

  15. Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence.

    PubMed

    Uranbileg, Baasanjav; Ikeda, Hitoshi; Kurano, Makoto; Enooku, Kenichiro; Sato, Masaya; Saigusa, Daisuke; Aoki, Junken; Ishizawa, Takeaki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    Although sphingosine 1-phosphate (S1P) has been reported to play an important role in cancer pathophysiology, little is known about S1P and hepatocellular carcinoma (HCC). To clarify the relationship between S1P and HCC, 77 patients with HCC who underwent surgical treatment were consecutively enrolled in this study. In addition, S1P and its metabolites were quantitated by LC-MS/MS. The mRNA levels of sphingosine kinases (SKs), which phosphorylate sphingosine to generate S1P, were increased in HCC tissues compared with adjacent non-HCC tissues. Higher mRNA levels of SKs in HCC were associated with poorer differentiation and microvascular invasion, whereas a higher level of SK2 mRNA was a risk factor for intra- and extra-hepatic recurrence. S1P levels, however, were unexpectedly reduced in HCC compared with non-HCC tissues, and increased mRNA levels of S1P lyase (SPL), which degrades S1P, were observed in HCC compared with non-HCC tissues. Higher SPL mRNA levels in HCC were associated with poorer differentiation. Finally, in HCC cell lines, inhibition of the expression of SKs or SPL by siRNA led to reduced proliferation, invasion and migration, whereas overexpression of SKs or SPL enhanced proliferation. In conclusion, increased SK and SPL mRNA expression along with reduced S1P levels were more commonly observed in HCC tissues compared with adjacent non-HCC tissues and were associated with poor differentiation and early recurrence. SPL as well as SKs may be therapeutic targets for HCC treatment.

  16. The effect of S1P receptor signaling pathway on the survival and drug resistance in multiple myeloma cells.

    PubMed

    Fu, Di; Li, Yingchun; Li, Jia; Shi, Xiaoyan; Yang, Ronghui; Zhong, Yuan; Wang, Huihan; Liao, Aijun

    2017-01-01

    Multiple myeloma (MM) remains incurable by conventional chemotherapy. Sphingosine-1-phosphate (S1P) receptor-mediated signaling has been recently demonstrated to have critical roles in cell survival and drug resistance in a number of hematological malignancies. To dissect the roles of S1P receptor pathway in MM, we systematically examined cell viability and protein expression associated with cell survival and drug resistance in MM cell lines upon treatment with either pathway activator (S1P) or inhibitor (FTY720). Our results reveal that FTY720 inhibits cell proliferation by downregulating expression of target genes, while S1P has an opposite effect. Knocking down of S1P receptor S1P5R results in a reduction of cell survival-related gene expression; however, it does not have impacts on expression of drug resistance genes. These results suggest that S1P signaling plays a role in cell proliferation and drug resistance in MM, and targeting this pathway will provide a new therapeutic direction for MM management.

  17. Development of a New Detection Scheme to Probe Predissociated Levels of the S_1 State of Acetylene

    NASA Astrophysics Data System (ADS)

    Jiang, Jun; Erickson, Trevor J.; Merer, Anthony; Field, Robert W.

    2016-06-01

    A new spectroscopic scheme has been developed to probe the predissociated levels of the S_1 state of acetylene. Our new scheme is based on detection of visible fluorescence that is a result of multi-photon excitation of acetylene (resonantly through single rovibronic S_1 levels). The new detection scheme is not subject to decreases in fluorescence quantum yield of S_1 levels that lie above the predissociation limit, and laser scatter-light can be easily eliminated by a long-pass filter with a cutoff in the visible range. For the S_1 predissociated levels, the new detection scheme offers much improved signal-to-noise ratio compared to the conventional laser-induced fluorescence technique, based on detection of UV fluorescence from the S_1 levels. The new method is also easier to implement than various H-atom detection schemes, which involve one additional laser of different wavelength than the excitation wavelength. Based on the power dependence and lifetime of the fluorescence signals, electronically excited C_2H and/or C_2 fragments are the likely emitters of the detected visible fluorescence. The new method is currently being used to extend the vibrational and rotational assignments of both gerade and ungerade levels of the S_1 state of acetylene in the region of the cis-trans isomerization barrier, >1000 cm-1 above the onset of S_1 predissociation.

  18. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial)

    PubMed Central

    Yoshida, M.; Ishiguro, M.; Ikejiri, K.; Mochizuki, I.; Nakamoto, Y.; Kinugasa, Y.; Takagane, A.; Endo, T.; Shinozaki, H.; Takii, Y.; Mochizuki, H.; Kotake, K.; Kameoka, S.; Takahashi, K.; Watanabe, T.; Watanabe, M.; Boku, N.; Tomita, N.; Nakatani, E.; Sugihara, K.

    2014-01-01

    Background S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur–uracil plus leucovorin (UFT/LV). Patients and methods Patients aged 20–80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80–120 mg/day on days 1–28 every 42 days; four courses) or UFT/LV (UFT: 300–600 mg/day and LV: 75 mg/day on days 1–28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. Results A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70–1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. Conclusion Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. ClinicalTrials.gov NCT00660894. PMID:24942277

  19. Alpha S1-casein polymorphisms in camel (Camelus dromedarius) and descriptions of biological active peptides and allergenic epitopes.

    PubMed

    Erhardt, Georg; Shuiep, El Tahir Salih; Lisson, Maria; Weimann, Christina; Wang, Zhaoxin; El Zubeir, Ibtisam El Yas Mohamed; Pauciullo, Alfredo

    2016-06-01

    Milk samples of 193 camels (Camelus dromedarius) from different regions of Sudan were screened for casein variability by isoelectric focusing. Kappa-casein and beta-casein were monomorphic, whereas three protein patterns named αs1-casein A, C, and D were identified. The major allele A revealed frequencies of 0.79 (Lahaoi), 0.75 (Shanbali), 0.90 (Arabi Khali), and 0.88 (Arabi Gharbawi) in the different ecotypes. CSN1S1*C shows a single G > T nucleotide substitution in the exon 5, leading to a non-synonymous amino acid exchange (p.Glu30 > Asp30) in comparison to CSN1S1*A and D. At cDNA level, no further single nucleotide polymorphisms could be identified in CSN1S1* A, C, and D, whereas the variants CSN1S1*A and CSN1S1*C are characterized by missing of exon 18 compared to the already described CSN1S1*B, as consequence of DNA insertion of 11 bp at intron 17 which alter the pre-mRNA spliceosome machinery. A polymerase chain-restriction fragment length polymorphism method (PCR-RFLP) was established to type for G > T nucleotide substitution at genomic DNA level. The occurrence and differences of IgE-binding epitopes and bioactive peptides between αs1-casein A, C, and D after digestion were analyzed in silico. The amino acid substitutions and deletion affected the arising peptide pattern and thus modifications between IgE-binding epitopes and bioactive peptides of the variants were found. The allergenic potential of these different peptides will be investigated by microarray immunoassay using sera from milk-sensitized individuals, as it was already demonstrated for bovine αs1-casein variants.

  20. Expression and secretion of the S-1 subunit and C180 peptide of pertussis toxin in Escherichia coli.

    PubMed Central

    Barbieri, J T; Moloney, B K; Mende-Mueller, L M

    1989-01-01

    The structural gene of the S-1 subunit of pertussis toxin (rS-1) and the catalytic C180 peptide of the S-1 subunit (C180 peptide) were independently subcloned downstream of the tac promoter in Escherichia coli. Both constructions included DNA encoding for the predicted leader sequence of the S-1 subunit which was inserted between the tac promoter and the structural gene. E. coli containing the plasmids encoding for rS-1 and C180 peptide produced a peptide that reacted with anti-pertussis toxin antibody and had a molecular weight corresponding to that of the cloned gene; some degradation of rS-1 was observed. Extracts of E. coli containing plasmids encoding for rS-1 and the C180 peptide possessed ADP-ribosyltransferase activity. Subcellular fractionation showed that both rS-1 and the C180 peptide were present in the periplasm, indicating that E. coli recognized the pertussis toxin peptide leader sequence. The protein sequence of the amino terminus of the C180 peptide was identical to that of authentic S-1 subunit produced by Bordetella pertussis, which showed that E. coli leader peptidase correctly processed the pertussis toxin peptide leader sequence. Two single amino acid substitutions at residue 26 (C180I-26) and residue 139 (C180S-139) which were previously shown to reduce ADP-ribosyltransferase activity were introduced into the C180 peptide. C180I-26 possessed approximately 1% of the NAD-glycohydrolase activity of the C180 peptide, suggesting that tryptophan 26 functions in the interaction of NAD with the C180 peptide. In contrast, C180S-139 possessed essentially the same level of NAD-glycohydrolase activity as the C180 peptide, suggesting that glutamic acid 139 does not function in the interaction of NAD but plays a role in a later step in the ADP-ribosyltransferase reaction. Images PMID:2546919

  1. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1.

    PubMed

    Schnute, Mark E; McReynolds, Matthew D; Kasten, Tom; Yates, Matthew; Jerome, Gina; Rains, John W; Hall, Troii; Chrencik, Jill; Kraus, Michelle; Cronin, Ciaran N; Saabye, Matthew; Highkin, Maureen K; Broadus, Richard; Ogawa, Shinji; Cukyne, Kristin; Zawadzke, Laura E; Peterkin, Vincent; Iyanar, Kaliapan; Scholten, Jeffrey A; Wendling, Jay; Fujiwara, Hideji; Nemirovskiy, Olga; Wittwer, Arthur J; Nagiec, Marek M

    2012-05-15

    SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P (sphingosine 1-phosphate). S1P promotes cell growth, survival and migration, and is a key regulator of lymphocyte trafficking. Inhibition of S1P signalling has been proposed as a strategy for treatment of inflammatory diseases and cancer. In the present paper we describe the discovery and characterization of PF-543, a novel cell-permeant inhibitor of SphK1. PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform. In 1483 head and neck carcinoma cells, which are characterized by high levels of SphK1 expression and an unusually high rate of S1P production, PF-543 decreased the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. In contrast with past reports that show that the growth of many cancer cell lines is SphK1-dependent, specific inhibition of SphK1 had no effect on the proliferation and survival of 1483 cells, despite a dramatic change in the cellular S1P/sphingosine ratio. PF-543 was effective as a potent inhibitor of S1P formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase is the major source of S1P in human blood. PF-543 is the most potent inhibitor of SphK1 described to date and it will be useful for dissecting specific roles of SphK1-driven S1P signalling.

  2. Individual variation of human S1P₁ coding sequence leads to heterogeneity in receptor function and drug interactions.

    PubMed

    Obinata, Hideru; Gutkind, Sarah; Stitham, Jeremiah; Okuno, Toshiaki; Yokomizo, Takehiko; Hwa, John; Hla, Timothy

    2014-12-01

    Sphingosine 1-phosphate receptor 1 (S1P₁), an abundantly-expressed G protein-coupled receptor which regulates key vascular and immune responses, is a therapeutic target in autoimmune diseases. Fingolimod/Gilenya (FTY720), an oral medication for relapsing-remitting multiple sclerosis, targets S1P₁ receptors on immune and neural cells to suppress neuroinflammation. However, suppression of endothelial S1P₁ receptors is associated with cardiac and vascular adverse effects. Here we report the genetic variations of the S1P₁ coding region from exon sequencing of >12,000 individuals and their functional consequences. We conducted functional analyses of 14 nonsynonymous single nucleotide polymorphisms (SNPs) of the S1PR1 gene. One SNP mutant (Arg¹²⁰ to Pro) failed to transmit sphingosine 1-phosphate (S1P)-induced intracellular signals such as calcium increase and activation of p44/42 MAPK and Akt. Two other mutants (Ile⁴⁵ to Thr and Gly³⁰⁵ to Cys) showed normal intracellular signals but impaired S1P-induced endocytosis, which made the receptor resistant to FTY720-induced degradation. Another SNP mutant (Arg¹³ to Gly) demonstrated protection from coronary artery disease in a high cardiovascular risk population. Individuals with this mutation showed a significantly lower percentage of multi-vessel coronary obstruction in a risk factor-matched case-control study. This study suggests that individual genetic variations of S1P₁ can influence receptor function and, therefore, infer differential disease risks and interaction with S1P₁-targeted therapeutics.

  3. Meta-analysis Exploring the Effectiveness of S-1-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

    PubMed

    Sun, Xin; Sun, Li; Zhang, Shu-Ling; Xiong, Zhi-Cheng; Ma, Jie-Tao; Han, Cheng-Bo

    2017-01-01

    S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

  4. TRAPPIST monitoring of comets C/2012 S1 (ISON) and C/2013 R1 (Lovejoy)

    NASA Astrophysics Data System (ADS)

    Opitom, C.; Jehin, E.; Manfroid, J.; Hutsemékers, D.; Gillon, M.

    2014-07-01

    We present the results of a dense photometric monitoring of comets C/2012 S1 (Ison) and C/2013 R1 (Lovejoy) using narrow-band cometary filters and the 60-cm TRAPPIST robotic telescope [1]. We were able to isolate the emission of the OH, NH, CN, C_2, and C_3 radicals for both comets as well as the dust continuum in four bands. By applying a Haser model [2] and fitting the observed profiles, we derive gas production rates. From the continuum bands, we computed the dust Afρ parameters [3]. We were able to follow the evolution of the gas and dust activity of these comets for weeks, looking for changes with the heliocentric distance, study the coma morphology, and analyze their composition and dust coma properties. Comet C/2012 S1 (ISON) was observed about three times a week from October 12 (r=1.43 au) to November 23, 2013. It was then at a heliocentric distance of 0.33 au, only five days before perihelion, when it disintegrated. This dense monitoring allowed us to detect fast changes of the cometary activity. We observed a slowly rising activity in October and early November, and two major outbursts around November 13 and November 19 [4], the gas and dust production rates being multiplied by at least a factor of five during each outburst and then slowly decreasing in the following days. These outbursts were correlated with changes in gas-production-rate ratios. The coma morphology study revealed strong jets in both gas and dust filters. Since the comet was very active in November, we were even able to detect OH jets in our images. Comet C/2013 R1 (Lovejoy) was observed before perihelion from September 9 (r=1.94 au) to November 16 (r=1.12 au), 2013 when the comet was too far North. We recovered the comet post-perihelion on February 13 (r=1.24 au), 2014 and planned to observe it until May (r=2.5 au) with narrow-band filters. We compare the evolution of gas and dust activity as well as the evolution of gas production rates ratios on both sides of perihelion. The

  5. Results from the Worldwide Coma Morphology Campaign for Comet ISON (C/2012 S1)

    NASA Astrophysics Data System (ADS)

    Samarasinha, Nalin H.

    2014-11-01

    Comet ISON (C/2012 S1) was predicted to be a bright comet in late 2013 because of its extremely small perihelion distance of 2.7 solar radii. In anticipation of the likely bonanza of scientific results, we coordinated a worldwide campaign (http://www.psi.edu/ison) to obtain both dust and gas images of the comet. During the campaign, we have received many hundreds of images primarily from amateur astronomers but also from a number of professionals.Comet ISON showed dust structure in its coma at large heliocentric distances before water became the primary sublimating gas. The Hubble Space Telescope (HST) observed a dust feature in the coma at a heliocentric distance of 4.15 AU in April 2013 (Li et al. 2013, ApJL, 779, article id. L3). The enhancement of continuum images taken by team members Nick Howes and Ernesto Guido at the 2-m Liverpool Telescope in May 2013 at different multiple epochs clearly showed the same dust feature (e.g., http://remanzacco.blogspot.com/2013/05/comet-c2012-s1-ison-update-may-20-2013.html). During the northern-hemisphere summer, the solar elongation of ISON became too small for ground-based observations. The comet was again observable starting in August 2013 as the solar elongation started to increase. These observations, at much smaller heliocentric distances than those described earlier, did not show the same dust feature. No unambiguous dust or gas features were seen until about two weeks prior to the perihelion and the comet’s demise (i.e., until mid November 2013). Based on the observations taken more than two weeks prior to the perihelion, we place upper limits on the radial extent of any possible dust feature. This and other results based on the coma morphology campaign will be discussed at the DPS 2014 meeting. The results from the analysis will be published in the future and will include the entire campaign.We thank many amateur and professional observers who contributed to this effort and all observers will be individually

  6. Magnetic order and magnon coherent state in double exchange s=1/2 lattices

    SciTech Connect

    Lopez-Aguilar, F.

    2010-02-15

    Starting from trial wave functions and by minimizing the total energy, we obtain the ground state (GS) of a magnetic system in which there is competition between two exchange interactions: one of them between localized and unlocalized spins and another one among the spins of a Heisenberg s=1/2 lattice. This analysis allows us to analyze directly a particular case of a magnetic ground state: a magnon gas whose collective wave function presents similarities with the coherent state of the electromagnetic field which is the basis for the laser. The Kondo coupling becomes concomitant with the external magnetic field which can control the number of magnons. The corresponding Zeeman effect provoked by the magnetic external field plus the Kondo interaction energy compete with the spin-spin Heisenberg exchange of the localized magnetic lattices. The fruit of the competition of these three interactions is the existence of a collective state which can be represented with an oscillation with one only frequency which has a minimum uncertainty and therefore it is a most similar quantum state to a classical wave. This collective state for determined crystal conditions, values of Kondo coupling strength, external B values and Heisenberg J{sub ij}-parameters tends to be a minimal energy state, and then, this coherent state, can transit to a magnon Bose-Einstein condensate (BEC). The passing from the minimal coherent state towards the BEC condensation is thermodynamically analyzed and we have deduced the critical temperature of this phase transition.

  7. Morphometric analysis of feedforward pathways from the primary somatosensory area (S1) of rats

    PubMed Central

    de Sá, A.L.; Bahia, C.P.; Correa, V.C.; Dias, I.A.; Batista, C.; Gomes-Leal, W.; Pinho, A.L.S.; Houzel, J.C.; Picanço-Diniz, C.W.; Pereira, A.

    2016-01-01

    We used biotinylated dextran amine (BDA) to anterogradely label individual axons projecting from primary somatosensory cortex (S1) to four different cortical areas in rats. A major goal was to determine whether axon terminals in these target areas shared morphometric similarities based on the shape of individual terminal arbors and the density of two bouton types: en passant (Bp) and terminaux (Bt). Evidence from tridimensional reconstructions of isolated axon terminal fragments (n=111) did support a degree of morphological heterogeneity establishing two broad groups of axon terminals. Morphological parameters associated with the complexity of terminal arbors and the proportion of beaded Bp vs stalked Bt were found to differ significantly in these two groups following a discriminant function statistical analysis across axon fragments. Interestingly, both groups occurred in all four target areas, possibly consistent with a commonality of presynaptic processing of tactile information. These findings lay the ground for additional work aiming to investigate synaptic function at the single bouton level and see how this might be associated with emerging properties in postsynaptic targets. PMID:27191604

  8. Hubble Space Telescope ACS/WFC Imaging Polarimetry of Comet ISON (C/2012 S1) (Invited)

    NASA Astrophysics Data System (ADS)

    Hines, D. C.; Videen, G.; Zubko, E.; Muinonen, K.; Shkuratov, Y.; Kaydash, V.; Knight, M. M.; Sitko, M.; Lisse, C. M.; Mutchler, M.; Hammer, D.; Yanamandra-Fisher, P. A.

    2013-12-01

    We present the first polarization images of Comet ISON (C/2012 S1) taken with the Hubble Space Telescope (HST) on UTC 2013 May 8 (r = 3.81 AU, Delta = 4.34 AU), when the phase angle was α = 12.25 degrees. Although this phase angle is approximately centered in the negative polarization branch for cometary dust, there is no evidence of a negative polarization circumnucleus halo region that has been observed in previous polarimetric images of short-period comets. Instead, the central region (~ 0.32 arcseconds = 6 pixels ≈ 1000 km) of the image shows a polarization amplitude p% = 2.0 - 2.5%, and a polarization direction that is approximately perpendicular to the scattering plane. Such positive polarization has been observed previously as a characteristic feature of cometary jets. The region beyond 1000 km, with sufficient signal-to-noise to make a polarization measurement (≤ 5000 km), shows a negative polarization amplitude p% ~ -1.8% that varies only slightly. Our results provide the first polarimetric observations of such a distant NIC at a small phase angle with sub-arcsecond spatial resolution

  9. Form factors of descendant operators: reduction to perturbed M (2 , 2 s + 1) models

    NASA Astrophysics Data System (ADS)

    Lashkevich, Michael; Pugai, Yaroslav

    2015-04-01

    In the framework of the algebraic approach to form factors in two-dimensional integrable models of quantum field theory we consider the reduction of the sine-Gordon model to the Φ13-perturbation of minimal conformal models of the M (2 , 2 s + 1) series. We find in an algebraic form the condition of compatibility of local operators with the reduction. We propose a construction that make it possible to obtain reduction compatible local operators in terms of screening currents. As an application we obtain exact multiparticle form factors for the compatible with the reduction conserved currents T ±2 k , Θ±(2 k-2), which correspond to the spin ±(2 k - 1) integrals of motion, for any positive integer k. Furthermore, we obtain all form factors of the operators T 2 k T -2 l , which generalize the famous operator. The construction is analytic in the s parameter and, therefore, makes sense in the sine-Gordon theory.

  10. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy

    PubMed Central

    Rolando, Monica; Escoll, Pedro; Nora, Tamara; Botti, Joëlle; Boitez, Valérie; Daniels, Craig; Abraham, Gilu; Stogios, Peter J.; Skarina, Tatiana; Christophe, Charlotte; Dervins-Ravault, Delphine; Cazalet, Christel; Hilbi, Hubert; Rupasinghe, Thusitha W. T.; Tull, Dedreia; McConville, Malcolm J.; Ong, Sze Ying; Hartland, Elizabeth L.; Codogno, Patrice; Levade, Thierry; Naderer, Thomas; Savchenko, Alexei; Buchrieser, Carmen

    2016-01-01

    Autophagy is an essential component of innate immunity, enabling the detection and elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to modulate autophagy through the action of effector proteins that are translocated into the host cell by the pathogen’s Dot/Icm type IV secretion system. Many of these effectors share structural and sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition by horizontal gene transfer from a eukaryotic host. Here we report that L. pneumophila translocates the effector protein sphingosine-1 phosphate lyase (LpSpl) to target the host sphingosine biosynthesis and to curtail autophagy. Our structural characterization of LpSpl and its comparison with human SPL reveals high structural conservation, thus supporting prior phylogenetic analysis. We show that LpSpl possesses S1P lyase activity that was abrogated by mutation of the catalytic site residues. L. pneumophila triggers the reduction of several sphingolipids critical for macrophage function in an LpSpl-dependent and -independent manner. LpSpl activity alone was sufficient to prevent an increase in sphingosine levels in infected host cells and to inhibit autophagy during macrophage infection. LpSpl was required for efficient infection of A/J mice, highlighting an important virulence role for this effector. Thus, we have uncovered a previously unidentified mechanism used by intracellular pathogens to inhibit autophagy, namely the disruption of host sphingolipid biosynthesis. PMID:26831115

  11. Photon Production from Proton-Antiproton Collisions at SQRT.S = 1.8TEV

    NASA Astrophysics Data System (ADS)

    Carter, Thomas Gordon

    1990-01-01

    The first measurement of low energy photon production from pp collisions at sqrt{s} = 1.8TeV is presented. The transverse momentum spectrum for photons is measured between 260 and 1500MeV/c. The < P_{t}> between those limits is 511 +/- 11MeV/c. The absolute photon production rate in the range P_{t} = 0-1500MeV/c for -0.48 >=q eta >=q 0.97 is found to be {dN _gammaover deta} = 3.44 +/- 0.15 +/- 0.34. The photon to charged pi ratio is measured in this range and found to be 1.40 +/- 0.07 +/- 0.20. For values of average charged particle multiplicity between 20 and 123, the value of < P_ {t}> varies linearly between 487MeV/c and 560MeV/c, the absolute production rate varies linearly between 1.55 and 10.1 and the photon to charge pi ratio remains constant. The eta to pi^0 ratio for the data sample is determined to be 0.33 +/- 0.19.

  12. Final report on the regional supplementary comparison APMP.AUV.A-S1

    NASA Astrophysics Data System (ADS)

    Plangsangmas, Virat; Leeudomwong, Surat; Scott, Andrew; Zhong, Bo; Huang, Yuchung

    2014-01-01

    A regional supplementary comparison APMP.AUV.A-S1 has been carried out for the measurement of sound pressure level, frequency and total distortion of a multi-frequency sound calibrator. The role of the Pilot laboratory was undertaken by the National Institute of Metrology (Thailand) (NIMT). The multi-frequency sound calibrator was circulated through thirteen National Metrology Institutes (NMIs). Two NMIs were added to the original time schedule after starting the circulation. The measurements took place between September 2008 and July 2010. This report includes the measurement results from all the participants. Supplementary Comparison Reference Values (SCRVs) have been determined from the results. Deviations from the SCRVs are mostly within declared expanded uncertainties. It has been found that a term for the inherent instability in this type of device needs to be included in any uncertainty budget, and a recommended minimum value of this has been given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCAUV, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  13. Observation of an Exotic Baryon with S=+1 in Photoproduction from the Proton

    SciTech Connect

    Valery Kubarovsky; Lei Guo; Dennis Weygand; Paul Stoler; Marco Battaglieri; Raffaella De Vita; Gary Adams; Ji Li; Mina Nozar; Carlos Salgado; Pawel Ambrozewicz; Eric Anciant; Marco Anghinolfi; Burin Asavapibhop; Gerard Audit; Thierry Auger; Harutyun AVAKIAN; Hovhannes Baghdasaryan; Jacques Ball; Steve Barrow

    2004-01-01

    The reaction {gamma}p {yields} {pi}{sup +} K{sup -} K{sup +}n was studied at Jefferson Lab using a tagged photon beam with an energy range of 3-5.47 GeV. A narrow baryon state with strangeness S = +1 and mass M = 1555 {+-} 10 MeV/c{sup 2} was observed in the nK{sup +} invariant mass spectrum. The peak's width is consistent with the CLAS resolution (FWHM = 26 MeV/c{sup 2}), and its statistical significance is 7.8 {+-} 1.0 {sigma}. A baryon with positive strangeness has exotic structure and cannot be described in the framework of the naive constituent quark model. The mass of the observed state is consistent with the mass predicted by a chiral soliton model for the {Theta}{sup +} baryon. In addition, the pK{sup +} invariant mass distribution was analyzed in the reaction {gamma} p {yields} K{sup -} K{sup +}p with high statistics in search of doubly-charged exotic baryon states. No resonance structures were found in this spectrum.

  14. The O(1S - 1D,3P) Line Intensity Ratio

    NASA Astrophysics Data System (ADS)

    Slanger, T. G.; Sharpee, B. D.; Cosby, P. C.; Minschwaner, K. R.; Siskind, D. E.

    2005-05-01

    The line intensity ratio of the two optically-forbidden atmospheric emissions, O(1S-1D) at 557.7 nm and O(1S-3P) at 297.2 nm, must be a single-valued number in the upper atmosphere because the upper level is common to both lines. The calculated transition probability ratio A(557.7)/A(297.2) is 16, by several authors, and the ratio found in the laboratory is significantly larger. Field observations require space-based instruments, in which case calibration between the two wavelengths is the critical issue. We circumvent this problem by using the O2 Herzberg I emission system as a bridge between the UV region below 310 nm and the ground-accessible region above that wavelength. These two spectral regions can be separately calibrated in terms of intensity, and the results of a disparate set of observations (satellite, rocket, ground-based) lead to A(557.7)/A(297.2) ratios that are consistently much smaller than the calculated value. These results have consequences for auroral and dayglow processes, and it is particularly important to ascertain the cause of the substantial difference between theory and observation.

  15. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy.

    PubMed

    Rolando, Monica; Escoll, Pedro; Nora, Tamara; Botti, Joëlle; Boitez, Valérie; Bedia, Carmen; Daniels, Craig; Abraham, Gilu; Stogios, Peter J; Skarina, Tatiana; Christophe, Charlotte; Dervins-Ravault, Delphine; Cazalet, Christel; Hilbi, Hubert; Rupasinghe, Thusitha W T; Tull, Dedreia; McConville, Malcolm J; Ong, Sze Ying; Hartland, Elizabeth L; Codogno, Patrice; Levade, Thierry; Naderer, Thomas; Savchenko, Alexei; Buchrieser, Carmen

    2016-02-16

    Autophagy is an essential component of innate immunity, enabling the detection and elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to modulate autophagy through the action of effector proteins that are translocated into the host cell by the pathogen's Dot/Icm type IV secretion system. Many of these effectors share structural and sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition by horizontal gene transfer from a eukaryotic host. Here we report that L. pneumophila translocates the effector protein sphingosine-1 phosphate lyase (LpSpl) to target the host sphingosine biosynthesis and to curtail autophagy. Our structural characterization of LpSpl and its comparison with human SPL reveals high structural conservation, thus supporting prior phylogenetic analysis. We show that LpSpl possesses S1P lyase activity that was abrogated by mutation of the catalytic site residues. L. pneumophila triggers the reduction of several sphingolipids critical for macrophage function in an LpSpl-dependent and -independent manner. LpSpl activity alone was sufficient to prevent an increase in sphingosine levels in infected host cells and to inhibit autophagy during macrophage infection. LpSpl was required for efficient infection of A/J mice, highlighting an important virulence role for this effector. Thus, we have uncovered a previously unidentified mechanism used by intracellular pathogens to inhibit autophagy, namely the disruption of host sphingolipid biosynthesis.

  16. Capture of Cometary Dust Grains in Impacts at 6.1 km s-1

    NASA Astrophysics Data System (ADS)

    Burchell, M. J.; Foster, N.; Kearsley, A.; Wozniakiewicz, P.

    2009-12-01

    The NASA Stardust mission to comet 81P/Wild 2 collected grains of cometary dust freshly ejected from the comet during a fly-by at a speed of 6.1 km s-1. These were captured on aluminum foils and in blocks of silica aerogel. The dust underwent a severe shock during capture. The nature of the shock process depends on the properties of the dust and the collecting media. On the aluminium, the shock process and impact damage is typical of that between high-density (or hard materials) at high velocity, resulting in craters lined with impactor residues. The peak shock pressures are estimated at 60-80 GPa. Two main crater types are seen, simple bowl shaped and multiple pit craters: these reflect the degree of consolidation of the original dust grain. Capture in the low density aerogel was via a more gradual slowing of the dust grains accompanied by a variety of effects on the grains (complete break up of weak grains vs. ablation of well consolidated grains). The relation between the structure of the dust grains and the resulting impact features in both collector materials is discussed.

  17. Specificity of an extracellular proteinase from Brevibacterium linens ATCC 9174 on bovine alpha s1-casein.

    PubMed Central

    Rattray, F P; Fox, P F; Healy, A

    1996-01-01

    The specificity of the extracellular proteinase from Brevibacterium linens ATCC 9174 on bovine alpha s1-casein was studied. Hydrolysis was monitored over time by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) and urea-PAGE. The major pH 4.6-soluble peptides were isolated by high-performance liquid chromatography and identified by N-terminal amino acid sequencing and mass spectrometry. The time course of peptide formation indicated that His-8-Gln-9, Ser-161-Gly-162, and either Gln-172-Tyr-173 or Phe-23-Phe-24 were the first, second, and third bonds cleaved, respectively. Other cleavage sites included Asn-19-Leu-20, Phe-32-Gly-33, Tyr-104-Lys-105, Leu-142-Ala-143, Phe-150-Arg-151, Gln-152-Phe-153, Leu-169-Gly-170, and Thr-171-Gln-172. The proteinase had a broad specificity for the amino acid residues at the P1 and P'1 positions but showed a preference for hydrophobic residues at the P2, P3, P4, P'2, P'3, and P'4 positions. PMID:8593051

  18. Photoisomerization dynamics of azobenzene in solution with S1 excitation: a femtosecond fluorescence anisotropy study.

    PubMed

    Chang, Chih-Wei; Lu, Ying-Chih; Wang, Tsai-Te; Diau, Eric Wei-Guang

    2004-08-18

    Measurements of anisotropy of femtosecond fluorescence after direct excitation of the S1(n,pi*) state of azobenzene in hexane and ethylene glycol solutions have been carried out to address the controversy about inversion and rotation in the mechanism of photoisomerization. The observed anisotropies in hexane decay to a nonzero asymptotic level with a relaxation period the same as that for slow decay of the corresponding biexponential transient; this effect is attributed to involvement of the out-of-plane CNNC-torsional motion on approach to a twisted conical intersection along the "rotation channel" that depolarizes the original in-plane transition moment. In contrast, when the rotational channel becomes substantially hindered in ethylene glycol, the anisotropies show no discernible decay feature, but the corresponding transients show prominent decays attributed to involvement of in-plane symmetric motions; the latter approach a planar-sloped conical intersection along a "concerted inversion channel" for efficient internal conversion through vibronic coupling. The proposed mechanism is consistent with theoretical calculations and rationalizes both results on quantum yields and ultrafast observations.

  19. PS-1/S1 picosecond streak camera application for multichannel laser system diagnostics

    SciTech Connect

    Garanin, S G; Bel'kov, S A; Rogozhnikov, G S; Rukavishnikov, N N; Romanov, V V; Voronich, I N; Vorob'ev, N S; Gornostaev, P B; Lozovoi, V I; Shchelev, M Ya

    2014-08-31

    A PS-1/S1 picosecond image-tube streak camera (ITSC) with slit scan (streak camera), developed and manufactured at the General Physics Institute RAS, has been used to measure the spatiotemporal characteristics of ultrashort laser pulses generated by a petawatt-power laser installation 'FEMTO' at the Institute of Laser Physics Research in Sarov. It is found that such a camera is suitable for measuring the spatial and temporal parameters of single laser pulses with an accuracy of about one picosecond. It is shown that the intensity time profile of a train of picosecond pulses may be precisely defined for the pulses separated in time by a few picoseconds. The camera allows the contrast of radiation to be determined with a high (no less than 10{sup 3}) accuracy; spatial distribution of the laser pulses can be measured with an accuracy of tens of microns, and the temporal separation of single laser pulses can be identified with an accuracy of 1 – 1.5 ps. (extreme light fields and their applications)

  20. Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide.

    PubMed

    Yang, Juanjuan; Liu, Yindi; Bi, Jing; Cai, Qixu; Liao, Xinli; Li, Wenqian; Guo, Chenyun; Zhang, Qian; Lin, Tianwei; Zhao, Yufen; Wang, Honghai; Liu, Jun; Zhang, Xuelian; Lin, Donghai

    2015-03-01

    Pyrazinamide (PZA) is a first-line drug for tuberculosis (TB) treatment and is responsible for shortening the duration of TB therapy. The mode of action of PZA remains elusive. RpsA, the ribosomal protein S1 of Mycobacterium tuberculosis (Mtb), was recently identified as a target of PZA based on its binding activity to pyrazinoic acid (POA), the active form of PZA. POA binding to RpsA led to the inhibition of trans-translation. However, the nature of the RpsA-POA interaction remains unknown. Key questions include why POA exhibits an exquisite specificity to RpsA of Mtb and how RpsA mutations confer PZA resistance. Here, we report the crystal structures of the C-terminal domain of RpsA of Mtb and its complex with POA, as well as the corresponding domains of two RpsA variants that are associated with PZA resistance. Structural analysis reveals that POA binds to RpsA through hydrogen bonds and hydrophobic interactions, mediated mainly by residues (Lys303, Phe307, Phe310 and Arg357) that are essential for tmRNA binding. Conformational changes induced by mutation or sequence variation at the C-terminus of RpsA abolish the POA binding activity. Our findings provide insights into the mode of action of PZA and molecular basis of PZA resistance associated with RpsA mutations.

  1. Constraints on the S=-1 meson-baryon interaction at NLO

    NASA Astrophysics Data System (ADS)

    Feijoo, A.; Magas, V. K.; Ramos, A.

    2017-03-01

    This work contains a study of the meson-baryon interaction in the S = -1 sector by means of a chiral SU(3) Lagrangian up to next-to-leading order (NLO) and implementing unitarization in coupled channels. In order to get more reliable values of the parameters which are present in the model, we performed several fits which take a large set of experimental scattering data in different two-body channels, threshold branching ratios, and the precise SIDDHARTA values of the energy shift and width of kaonic hidrogen into consideration. In previous studies, we had shown that the K- p → KΞ reactions are especially sensitive to the next to Weinberg-Tomozawa (WT) corrections in the hierarchy. In addition, we pointed out the need to employ processes which are described by pure isospin amplitudes as a tool to discern which models are more realistic among those which give small values for the χ2 in the fits. Following the former suggestion, we present results which include data from K- p → ηΛ, ηΣ reactions which have pure isospin I = 0 and I = 1 component respectively. Finally, to check the goodness of the new obtained parametrization of the model, we present a prediction for another process that filters the I = 1 isospin component: the pure I = 1 K_L^ - p \\to {K^ + }{Ξ^0} reaction which could be measured at the proposed secondary K0L beam at Jlab.

  2. Incommensurate correlations in a S=1/2 4-leg quantum spin tube

    NASA Astrophysics Data System (ADS)

    Zheludev, Andrey; Garlea, Ovidiu; Regnault, Louis-Pierre; Habicht, Klaus

    2008-03-01

    Inelastic neutron scattering is used to investigate magnetic excitations in the quasi-one- dimensional quantum spin-liquid system Cu2Cl4-D8C4SO2. Contrary to previously conjectured models, the appropriate Heisenberg Hamiltonian is equivalent to that of a S=1/2 4-leg spin-tube with almost perfect one dimensionality and no bond alternation [1]. A partial geometric frustration of rung interactions induces a small incommensurability of short-range spin correlations. In high magnetic fields, a Bose-Einstein condensation of magnons induces a quantum phase transition to a incommensurate helimagnetic ordered state. Research at ORNL was funded by the United States Department of Energy, Office of Basic Energy Sciences- Materials Science, under Contract No. DE-AC05-00OR22725 with UT-Battelle, LLC. [1] V. O. Garlea , A. Zheludev, L.-P. Regnault, J.-H. Chung, Y. Qiu, M. Boehm, K. Habicht and M. Meissner, Phys. Rev. Lett., in press (2007); arXiv:0710.0891.

  3. Fermionic Representation of a Spin S chain Using subalgebra of SU(2S+1)

    NASA Astrophysics Data System (ADS)

    Duki, Solomon F.; Yu, Yi-Kuo

    2014-03-01

    Quantum mechanical spins behave neither as pure bosonic nor as pure fermionic operators. Over the years many different kinds of important mappings have been introduced that transform spins systems in to either multi-bosonic or multi-fermionic systems. These mappings have often successfully transformed some of the most difficult many body problems into simpler ones. Moreover, because symmetries that are hidden in one representation can be manifested in other representations, such mappings are also helpful in uncovering hidden symmetries in physical problems. Examples of such transformations include the Holstein-Primakoff, the Schwinger bosons, the Matsubara-Matsuda, and the Jordan-Wigner transformations. Despite their success for low dimensional systems and at smaller values of spins, these transformations become ineffective in reducing the degree of difficulty of correlated systems when the system dimension increase or when the underlying system has a higher spin values. In the context of a spin chain, we introduce a new spin fermion transformation for arbitrary spin S using the subalgebra of the bigger su(2S+1) algebra and discuss its potential applications in physical problems. This research was supported by the Intramural Research Program of the NIH, National Library of Medicine.

  4. miR-127 enhances myogenic cell differentiation by targeting S1PR3.

    PubMed

    Zhai, Lili; Wu, Rimao; Han, Wanhong; Zhang, Yong; Zhu, Dahai

    2017-03-30

    MicroRNAs (miRNAs) have recently been implicated in muscle stem cell function. miR-127 is known to be predominantly expressed in skeletal muscle, but its roles in myogenic differentiation and muscle regeneration are unknown. Here, we show that miR-127 is upregulated during C2C12 and satellite cell (SC) differentiation and, by establishing C2C12 cells stably expressing miR-127, demonstrate that overexpression of miR-127 in C2C12 cells enhances myogenic cell differentiation. To investigate the function of miR-127 during muscle development and regeneration in vivo, we generated miR-127 transgenic mice. These mice exhibited remarkably accelerated muscle regeneration compared with wild-type mice by promoting SC differentiation. Mechanistically, we demonstrated that the gene encoding sphingosine-1-phosphate receptor 3 (S1PR3), a G-protein-coupled receptor for sphingosine-1-phosphate, is a target of miR-127 required for its function in promoting myogenic cell differentiation. Importantly, overexpression of miR-127 in muscular dystrophy model mdx mice considerably ameliorated the disease phenotype. Thus, our findings suggest that miR-127 may serve as a potential therapeutic target for the treatment of skeletal muscle disease in humans.

  5. Observation of orbiting resonances in He(3S1) + NH3 Penning ionization

    NASA Astrophysics Data System (ADS)

    Jankunas, Justin; Jachymski, Krzysztof; Hapka, Michał; Osterwalder, Andreas

    2015-04-01

    Resonances are among the clearest quantum mechanical signatures of scattering processes. Previously, shape resonances and Feshbach resonances have been observed in inelastic and reactive collisions involving atoms or diatomic molecules. Structure in the integral cross section has been observed in a handful of elastic collisions involving polyatomic molecules. The present paper presents the observation of shape resonances in the reactive scattering of a polyatomic molecule, NH3. A merged-beam study of the gas phase He(3S1) + NH3 Penning ionization reaction dynamics is described in the collision energy range 3.3 μeV < Ecoll < 10 meV. In this energy range, the reaction rate is governed by long-range attraction. Peaks in the integral cross section are observed at collision energies of 1.8 meV and 7.3 meV and are assigned to ℓ = 15,16 and ℓ = 20,21 partial wave resonances, respectively. The experimental results are well reproduced by theoretical calculations with the short-range reaction probability Psr = 0.035. No clear signature of the orbiting resonances is visible in the branching ratio between NH3+ and NH2+ formation.

  6. HUBBLE SPACE TELESCOPE OBSERVATIONS OF THE NUCLEUS OF COMET C/2012 S1 (ISON)

    SciTech Connect

    Lamy, Philippe L.; Toth, Imre; Weaver, Harold A.

    2014-10-10

    We report on the analysis of several sequences of broadband visible images of comet C/2012 S1 (ISON) taken with the Wide Field Camera 3 of the Hubble Space Telescope on 2013 April 10, May 8, October 9, and November 1 in an attempt to detect and characterize its nucleus. Whereas the overwhelming coma precluded the detection of the nucleus in the first two sequences, the contrast was sufficient in early October to unambiguously retrieve the signal from the nucleus. Two images taken within a few minutes led to similar V magnitudes for the nucleus of 21.97 and 22.0 with a 1σ uncertainty of 0.065. Assuming a standard value for the geometric albedo (0.04) and a linear phase function with a coefficient of 0.04 mag deg{sup –1}, these V values imply that the nucleus radius is 0.68 ± 0.02 km. Although this result does depend on these two assumptions, we argue that the radius most likely lies in the range 0.6-0.9 km. This result is consistent with the constraints derived from the water production rates reported by Combi et al. The last sequence of images in 2013 November revealed temporal variation of the innermost coma. If attributed to a single rotating jet, this coma brightness variation suggests the rotational period of the nucleus may be close to ∼10.4 hr.

  7. Diel vertical migration of zooplankton at the S1 biogeochemical mooring revealed from acoustic backscattering strength

    NASA Astrophysics Data System (ADS)

    Inoue, Ryuichiro; Kitamura, Minoru; Fujiki, Tetsuichi

    2016-02-01

    We examined the diel vertical migration of zooplankton by using the backscatter strength obtained from moored acoustic Doppler current profilers at mooring site S1 in the North Pacific subtropical gyre. There was seasonal variability in the vertical distribution and migration of the high-backscatter layers in that they became deeper than the euphotic zone (<100 m) in winter and were confined above this depth in other seasons. Seasonal changes in daylight hours also affected the timing of the diel migration. We found that lunar cycles affected vertical distributions of zooplankton near the surface by changing the light intensity. Physical events, such as mixed-layer deepening and restratification and the passage of a mesoscale eddy, also affected zooplankton behavior possibly by changing food environment in the euphotic zone. Since the comparison with net samples indicated that the backscatter likely represents the bulk biomass, the accuracy of biomass estimates based on net samples could be influenced by the high temporal variability of zooplankton distributions.

  8. Dephasing of localized excitons in CdS1-xSex mixed crystals

    NASA Astrophysics Data System (ADS)

    Schwab, H.; Lyssenko, V. G.; Hvam, J. M.; Klingshirn, C.

    1991-08-01

    We performed photon-echo experiments in the alloy semiconductor CdS1-xSex to study the influence of the localization depth on the dephasing of localized excitons. It was found that the laser pulse width critically influences the measured values for the phase coherence time T2, as well as the observed behavior of the investigated localized states. At TL=1.8 K T2 increases from 400+/-40 ps on the high-energy side of the luminescence band, close to the extended states, up to 2.2+/-0.7 ns on the low-energy side of this emission band for deeply localized states. These extremely large values are comparable with the lifetime of these resonantly excited states. If we raise the lattice temperature TL the scattering rate increases significantly. We find T2 to be 1.5 ns at 2.208 eV and TL=5 K and T2=80 ps at 15 K at the same energy. At shorter wavelengths the influence of the temperature is less pronounced.

  9. Comet C/2012 S1 (ISON): Final observations from the Deep Impact spacecraft

    NASA Astrophysics Data System (ADS)

    Farnham, T. L.; Kelley, M. S. P.; A'Hearn, M. F.; Feaga, L. M.; Bodewits, D.; Sunshine, J. M.; Wellnitz, D. D.; Wissler, S.

    2017-03-01

    The Deep Impact spacecraft observed comet C/2012 S1 (ISON) between 17 January and 10 March 2013 when the comet was ∼5 AU from the Sun. Continuous, high-cadence, images spanning as much as 6 days at a time, and high-cadence IR spectral scans spanning 2 days, represent the most intensive set of observations available from the early part of ISON's apparition. These observations were used to investigate the comet's detailed behavior, including variability in the lightcurve and changes in the coma morphology. ISON experienced a gradual brightening throughout this time period, with A(0)fρ increasing from 1150 cm in January to 1430 cm in March. Although no periodic variability was detected to a level <3%, DI did record several events showing the comet spontaneously brightening by 10-15% for several hours, indicating that the comet was experiencing spontaneous bursts of enhanced activity. These small outbursts may be the result of residual pockets of the volatiles that drove the rapid brightening seen between 8 and 5 AU. No changes were detected in the coma morphology over the course of the observations, and no gas emission was detected in either the narrowband comet gas filters or the IR spectra.

  10. Specificity of an extracellular proteinase from Brevibacterium linens ATCC 9174 on bovine alpha s1-casein.

    PubMed

    Rattray, F P; Fox, P F; Healy, A

    1996-02-01

    The specificity of the extracellular proteinase from Brevibacterium linens ATCC 9174 on bovine alpha s1-casein was studied. Hydrolysis was monitored over time by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) and urea-PAGE. The major pH 4.6-soluble peptides were isolated by high-performance liquid chromatography and identified by N-terminal amino acid sequencing and mass spectrometry. The time course of peptide formation indicated that His-8-Gln-9, Ser-161-Gly-162, and either Gln-172-Tyr-173 or Phe-23-Phe-24 were the first, second, and third bonds cleaved, respectively. Other cleavage sites included Asn-19-Leu-20, Phe-32-Gly-33, Tyr-104-Lys-105, Leu-142-Ala-143, Phe-150-Arg-151, Gln-152-Phe-153, Leu-169-Gly-170, and Thr-171-Gln-172. The proteinase had a broad specificity for the amino acid residues at the P1 and P'1 positions but showed a preference for hydrophobic residues at the P2, P3, P4, P'2, P'3, and P'4 positions.

  11. Understanding the physiological roles of polyhydroxybutyrate (PHB) in Rhodospirillum rubrum S1 under aerobic chemoheterotrophic conditions.

    PubMed

    Narancic, Tanja; Scollica, Elisa; Kenny, Shane T; Gibbons, Helena; Carr, Eibhlin; Brennan, Lorraine; Cagney, Gerard; Wynne, Kieran; Murphy, Cormac; Raberg, Matthias; Heinrich, Daniel; Steinbüchel, Alexander; O'Connor, Kevin E

    2016-10-01

    Polyhydroxybutyrate (PHB) is an important biopolymer accumulated by bacteria and associated with cell survival and stress response. Here, we make two surprising findings in the PHB-accumulating species Rhodospirillum rubrum S1. We first show that the presence of PHB promotes the increased assimilation of acetate preferentially into biomass rather than PHB. When R. rubrum is supplied with (13)C-acetate as a PHB precursor, 83.5 % of the carbon in PHB comes from acetate. However, only 15 % of the acetate ends up in PHB with the remainder assimilated as bacterial biomass. The PHB-negative mutant of R. rubrum assimilates 2-fold less acetate into biomass compared to the wild-type strain. Acetate assimilation proceeds via the ethylmalonyl-CoA pathway with (R)-3-hydroxybutyrate as a common intermediate with the PHB pathway. Secondly, we show that R. rubrum cells accumulating PHB have reduced ribulose 1,5-bisphosphate carboxylase (RuBisCO) activity. RuBisCO activity reduces 5-fold over a 36-h period after the onset of PHB. In contrast, a PHB-negative mutant maintains the same level of RuBisCO activity over the growth period. Since RuBisCO controls the redox potential in R. rubrum, PHB likely replaces RuBisCO in this role. R. rubrum is the first bacterium found to express RuBisCO under aerobic chemoheterotrophic conditions.

  12. Extending the Family of V(4+) S=(1/2) Kagome Antiferromagnets.

    PubMed

    Clark, Lucy; Aidoudi, Farida H; Black, Cameron; Arachchige, Kasun S A; Slawin, Alexandra M Z; Morris, Russell E; Lightfoot, Philip

    2015-12-14

    The ionothermal synthesis, structure, and magnetic susceptibility of a novel inorganic-organic hybrid material, imidazolium vanadium(III,IV) oxyfluoride [C3 H5 N2 ][V9 O6 F24 (H2 O)2 ] (ImVOF) are presented. The structure consists of inorganic vanadium oxyfluoride slabs with kagome layers of V(4+) S=${{ 1/2 }}$ ions separated by a mixed valence layer. These inorganic slabs are intercalated with imidazolium cations. Quinuclidinium (Q) and pyrazinium (Pyz) cations can also be incorporated into the hybrid structure type to give QVOF and PyzVOF analogues, respectively. The highly frustrated topology of the inorganic slabs, along with the quantum nature of the magnetism associated with V(4+) , means that these materials are excellent candidates to host exotic magnetic ground states, such as the highly sought quantum spin liquid. Magnetic susceptibility measurements of all samples suggest an absence of conventional long-range magnetic order down to 2 K despite considerable antiferromagnetic exchange.

  13. The weak measurement process and the weak value of spin for metastable helium 23S1

    NASA Astrophysics Data System (ADS)

    Monachello, Vincenzo; Barker, Peter; Flack, Robert; Hiley, Basil

    2016-05-01

    An experiment is being designed and constructed in order to measure the weak value of spin for an atomic system. The principle of the ``weak measurement'' process was first proposed by Aharonov, Albert and Vaidman, and describes a scenario in which a system is weakly coupled to a pointer between well-defined pre- and post-selected states. This experiment will utilise a pulsed supersonic beam of spin-1 metastable Helium (He*) atoms in the 23S1 state. The spin of the pre-selected He* atoms will be weakly coupled to its centre-of-mass. During its flight, the atomic beam will be prepared in a desired quantum state and travel through two inhomogeneous magnets (weak and strong) which both comprise the ``weak measurement'' process. The deviation of the post-selected ms = + 1 state as measured using a micro-channel plate, phosphor screen and CCD camera setup will allow for the determination of the weak value of spin. This poster will report on the methods used and the experimental realisation.

  14. Region 9: Arizona Adequate Letter (10/14/2003)

    EPA Pesticide Factsheets

    This is a letter from Jack P. Broadben,. Director, to Nancy Wrona and Dennis Smith informing them that Maricopa County's motor vehicle emissions budgets in the 2003 MAGCO Maintenance Plan are adequate for transportation conformity purposes.

  15. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions of... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44...

  16. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions of... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44...

  17. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions of... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44...

  18. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions of... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44...

  19. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions of... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44...

  20. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... without interruption by means of the traditional kinship system of the appropriate Indian tribe or Native... following types of evidence: Geographical, kinship, biological, archeological, anthropological,...

  1. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... without interruption by means of the traditional kinship system of the appropriate Indian tribe or Native... following types of evidence: Geographical, kinship, biological, archeological, anthropological,...

  2. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... without interruption by means of the traditional kinship system of the appropriate Indian tribe or Native... following types of evidence: Geographical, kinship, biological, archeological, anthropological,...

  3. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... without interruption by means of the traditional kinship system of the appropriate Indian tribe or Native... following types of evidence: Geographical, kinship, biological, archeological, anthropological,...

  4. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... without interruption by means of the traditional kinship system of the appropriate Indian tribe or Native... following types of evidence: Geographical, kinship, biological, archeological, anthropological,...

  5. The growth of epitaxial single crystal PbS 1-xSe x films by hot wall evaporation

    NASA Astrophysics Data System (ADS)

    Neuelmann, R.; Marino, A.; Reichelt, K.

    1983-12-01

    Heteroepitaxial films of semiconducting PbS 1- xSe x on rock salt and mica substrates have been prepared and studied. The films have good crystalline perfection but have low electron mobilities, probably due to deviations from stoichiometry.

  6. Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

    SciTech Connect

    Gordon, Wendy R.; Vardar-Ulu, Didem; L'Heureux, Sarah; Ashworth, Todd; Malecki, Michael J.; Sanchez-Irizarry, Cheryll; McArthur, Debbie G.; Histen, Gavin; Mitchell, Jennifer L.; Aster, Jon C.; Blacklow, Stephen C.

    2009-09-25

    Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia. The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity. S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which ligand-binding or

  7. Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

    PubMed Central

    Gordon, Wendy R.; Vardar-Ulu, Didem; L'Heureux, Sarah; Ashworth, Todd; Malecki, Michael J.; Sanchez-Irizarry, Cheryll; McArthur, Debbie G.; Histen, Gavin; Mitchell, Jennifer L.; Aster, Jon C.; Blacklow, Stephen C.

    2009-01-01

    Background Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia. Principal Findings The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity. Conclusions/Significance S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with

  8. Potential of MuS1 Transgenic Tobacco for Phytoremediation of the Urban Soils Contaminated with Cadmium

    NASA Astrophysics Data System (ADS)

    Kim, K. H.; Kim, Y. N.; Kim, S. H.

    2010-05-01

    Urban soils are prone to contamination by trace elements such as Cd, Cu, Pb and Zn. Phytoremediation is one of the attractive remediation methods for soils contaminated with trace elements due to its non-destructive and environmentally-friendly characteristic. Scientists have tried to find hyper-accumulator plants in nature or to develop transgenic plant through genetic engineering. This study was carried out to identify a potential of MuS1 transgenic tobacco for phytoremediation of the urban soils contaminated with Cd. MuS1 is known as a multiple stress related gene with several lines. The previous study using RT-PCR showed that the expression of MuS1 gene in tobacco plant induced tolerance to Cd stress. For this study, MuS1 transgenic tobacco and wild-type tobacco (control) were cultivated in a hydroponic system treated with Cd (0, 50, 100 and 200μM Cd) for 3 weeks. At harvest, both tobacco and nutrient solution were collected and were analyzed for Cd. Effect of Cd treatment on morphological change of the tobacco leaves was also observed by variable-pressure scanning electron microscopy (VP-SEM). The tolerance of MuS1 transgenic tobacco to Cd stress was better than that of wild-type tobacco at all Cd levels. Especially, wild-type tobacco showed chlorosis and withering with 200μM Cd treatment, whereas MuS1 transgenic tobacco gradually recovered from Cd damage. Wild-type tobacco accumulated more Cd (4.65mg per plant) than MuS1 transgenic tobacco (2.37mg per plant) with 200μM Cd treatment. Cd translocation rate from root to leaves was 81.8 % for wild-type tobacco compared to 37.1 % for MuS1 transgenic tobacco. Result of VP-SEM showed that the number of trichome in the leaves for wild-type tobacco increased in comparison with that for untreated samples after 3 weeks, while that for MuS1 transgenic tobacco was not changed by Cd treatment. Results showed that the mechanism of the recovery of the MuS1 tobacco plant was not by high level of Cd uptake and accumulation

  9. The elusive S2 state, the S1/S2 splitting, and the excimer states of the benzene dimer.

    PubMed

    Balmer, Franziska A; Trachsel, Maria A; van der Avoird, Ad; Leutwyler, Samuel

    2015-06-21

    We observe the weak S0 → S2 transitions of the T-shaped benzene dimers (Bz)2 and (Bz-d6)2 about 250 cm(-1) and 220 cm(-1) above their respective S0 → S1 electronic origins using two-color resonant two-photon ionization spectroscopy. Spin-component scaled (SCS) second-order approximate coupled-cluster (CC2) calculations predict that for the tipped T-shaped geometry, the S0 → S2 electronic oscillator strength fel(S2) is ∼10 times smaller than fel(S1) and the S2 state lies ∼240 cm(-1) above S1, in excellent agreement with experiment. The S0 → S1 (ππ(∗)) transition is mainly localized on the "stem" benzene, with a minor stem → cap charge-transfer contribution; the S0 → S2 transition is mainly localized on the "cap" benzene. The orbitals, electronic oscillator strengths fel(S1) and fel(S2), and transition frequencies depend strongly on the tipping angle ω between the two Bz moieties. The SCS-CC2 calculated S1 and S2 excitation energies at different T-shaped, stacked-parallel and parallel-displaced stationary points of the (Bz)2 ground-state surface allow to construct approximate S1 and S2 potential energy surfaces and reveal their relation to the "excimer" states at the stacked-parallel geometry. The fel(S1) and fel(S2) transition dipole moments at the C2v-symmetric T-shape, parallel-displaced and stacked-parallel geometries are either zero or ∼10 times smaller than at the tipped T-shaped geometry. This unusual property of the S0 → S1 and S0 → S2 transition-dipole moment surfaces of (Bz)2 restricts its observation by electronic spectroscopy to the tipped and tilted T-shaped geometries; the other ground-state geometries are impossible or extremely difficult to observe. The S0 → S1/S2 spectra of (Bz)2 are compared to those of imidazole ⋅ (Bz)2, which has a rigid triangular structure with a tilted (Bz)2 subunit. The S0 → S1/ S2 transitions of imidazole-(benzene)2 lie at similar energies as those of (Bz)2, confirming our assignment of the

  10. Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect.

    PubMed

    Adamson, R H; Clark, J F; Radeva, M; Kheirolomoom, A; Ferrara, K W; Curry, F E

    2014-04-01

    Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (Ps)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with Ps when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 ± 46 nM) was near the normal plasma value at 37 °C and established a stable baseline Ps (0.9 ± 0.4 × 10(-6) cm/s). Ringer solution perfusate contained 52 ± 8 nM S1P and increased Ps more than 10-fold (16.1 ± 3.9 × 10(-6) cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium.

  11. The S1 Helix Critically Regulates the Finely-tuned Gating of Kv11.1 Channels.

    PubMed

    Phan, Kevin; Ng, Chai Ann; David, Erikka; Shishmarev, Dmitry; Kuchel, Philip W; Vandenberg, Jamie I; Perry, Matthew D

    2017-03-09

    Congenital mutations in the cardiac Kv11.1 channel can cause long QT syndrome type 2 (LQTS2), a heart rhythm disorder associated with sudden cardiac death. Mutations act either by reducing protein expression at the membrane, and/or by perturbing the intricate gating properties of Kv11.1 channels. A number of clinical LQTS2-associated mutations have been reported in the first transmembrane segment (S1) of Kv11.1 channels but the role of this region of the channel is largely unexplored. In part this is due to problems defining the extent of the S1 helix, as a consequence of its low sequence homology with other Kv family members. Here we used NMR spectroscopy and electrophysiological characterization to show that the S1 of Kv11.1 channels extends seven helical turns, from Pro405 to Phe431, and is flanked by unstructured loops. Functional analysis suggests that pre-S1 loop residues His402 and Tyr403 play an important role in regulating the kinetics and voltage dependence of channel activation and deactivation. Multiple residues within the S1 helix also play an important role in fine-tuning the voltage dependence of activation, regulating slow deactivation, and modulating C-type inactivation of Kv11.1 channels. Analyses of LQTS2-associated mutations in the pre-S1 loop or S1 helix of Kv11.1 channels demonstrate perturbations to both protein expression and most gating transitions. Thus S1 region mutations would reduce both the action potential repolarizing current passed by Kv11.1 channels in cardiac myocytes, as well as the current passed in response to premature depolarizations that normally helps protect against the formation of ectopic beats.

  12. Symmetry control of radiative decay in linear polyenes: low barriers for isomerization in the S1 state of hexadecaheptaene.

    PubMed

    Christensen, Ronald L; Galinato, Mary Grace I; Chu, Emily F; Fujii, Ritsuko; Hashimoto, Hideki; Frank, Harry A

    2007-02-14

    The room temperature absorption and emission spectra of the 4-cis and all-trans isomers of 2,4,6,8,10,12,14-hexadecaheptaene are almost identical, exhibiting the characteristic dual emissions S1-->S0 (21Ag- --> 11Ag-) and S2-->S0 (11Bu+ --> 11Ag-) noted in previous studies of intermediate length polyenes and carotenoids. The ratio of the S1-->S0 and S2-->S0 emission yields for the cis isomer increases by a factor of approximately 15 upon cooling to 77 K in n-pentadecane. In contrast, for the trans isomer this ratio shows a 2-fold decrease with decreasing temperature. These results suggest a low barrier for conversion between the 4-cis and all-trans isomers in the S1 state. At 77 K, the cis isomer cannot convert to the more stable all-trans isomer in the 21Ag- state, resulting in the striking increase in its S1-->S0 fluorescence. These experiments imply that the S1 states of longer polyenes have local energy minima, corresponding to a range of conformations and isomers, separated by relatively low (2-4 kcal) barriers. Steady state and time-resolved optical measurements on the S1 states in solution thus may sample a distribution of conformers and geometric isomers, even for samples represented by a single, dominant ground state structure. Complex S1 potential energy surfaces may help explain the complicated S2-->S1 relaxation kinetics of many carotenoids. The finding that fluorescence from linear polyenes is so strongly dependent on molecular symmetry requires a reevaluation of the literature on the radiative properties of all-trans polyenes and carotenoids.

  13. Anti-S1P antibody as a novel therapeutic strategy for VEGFR TKI resistant renal cancer

    PubMed Central

    Bullock, Andrea J.; Callea, Marcella; Shah, Harleen; Song, Jiaxi; Moreno, Kelli; Visentin, Barbara; Deutschman, Douglas; Alsop, David C.; Atkins, Michael B.; Mier, James W.; Signoretti, Sabina; Bhasin, Manoj; Sabbadini, Roger A.; Bhatt, Rupal S.

    2015-01-01

    Purpose VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic RCC. However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for both patients with TKI naïve or resistant RCC. Experimental design In this study, we performed transcriptome analysis of VEGFR TKI resistant tumors in a murine model and discovered that the SPHK/S1P pathway is upregulated at the time of resistance. We tested S1P pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC. Results Resistant tumors expressed several hypoxia regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC suggesting that human RCC behavior could, in part, be due to over-production of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI. Conclusions Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment naïve RCC and also in the setting of resistance to VEGFR TKI therapy. PMID:25589614

  14. Effects of aging on properties of the local circuit in rat primary somatosensory cortex (S1) in vitro.

    PubMed

    Hickmott, Peter; Dinse, Hubert

    2013-10-01

    During aging receptive field properties degrade, the ability of the circuit to process temporal information is impaired and behaviors mediated by the circuit can become impaired. These changes are mediated by changes in the properties of neural circuits, particularly the balance of excitation and inhibition, the intrinsic properties of neurons, and the anatomy of connections in the circuit. In this study, properties of thalamorecipient pyramidal neurons in layer 3 were examined in the hindpaw region of rat primary somatosensory cortex (S1) in vitro. Excitatory and inhibitory postsynaptic currents (IPSCs) resulting from trains of electrical stimulation of thalamocortical afferents were recorded. Excitatory postsynaptic currents were larger in old S1, but showed no difference in temporal dynamics; IPSCs showed significantly less suppression across the train in old S1, partly due to a decrease in GABAB signaling. Neurons in old S1 were more likely to exhibit burst firing, due to an increase in T-current. Significant differences in dendritic morphology were also observed in old S1, accompanied by a decrease in dendritic spine density. These data directly demonstrate changes in the properties of the thalamorecipient circuit in old S1 and help to explain the changes observed in responses during aging.

  15. Role of JAK-STAT pathway in reducing cardiomyocytes hypoxia/reoxygenation injury induced by S1P postconditioning.

    PubMed

    Wang, Yuqing; Wang, Dongfei; Zhang, Lizhi; Ye, Fangyu; Li, Mengmeng; Wen, Ke

    2016-08-05

    This experiment was designed to explore the protection of sphingosine1-phosphate (S1P) postconditioning on rat myocardial cells injured by hypoxia/reoxygenation acting via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signal pathway. The data showed that S1P could significantly increase cell viability, lower the rate of apoptosis, decrease the content of lactate dehydrogenase (LDH) and caspase3 activity in the culture medium, increase the activity of total superoxide dismutase (T-SOD) and manganese superoxide dismutase (Mn-SOD), reduce the loss of mitochondrial membrane potential and the fluorescence intensity of intracellular calcium, as well as increase the phosphorylation of JAK2 and STAT3 in comparison with the H/R group. When the JAK inhibitor AG490 or the STAT inhibitor stattic were added, the effects of S1P were inhibited. Our date shows that S1P protects H9c2 cells from hypoxia/reoxygenation injury and that the protection by S1P was inhibited by AG490 and stattic. Therefore S1P protects H9c2 cells against hypoxia/reoxygenation injury via the JAK-STAT pathway.

  16. Molecular cloning and expression of an encoding galactinol synthase gene (AnGolS1) in seedling of Ammopiptanthus nanus

    PubMed Central

    Liu, YuDong; Zhang, Li; Chen, LiJing; Ma, Hui; Ruan, YanYe; Xu, Tao; Xu, ChuanQiang; He, Yi; Qi, MingFang

    2016-01-01

    Based on the galactinol synthase (AnGolS1) fragment sequence from a cold-induced Suppression Subtractive Hybridization (SSH) library derived from Ammopiptanthus nanus (A. nanus) seedlings, AnGolS1 mRNA (including the 5′ UTR and 3′ UTR) (GenBank accession number: GU942748) was isolated and characterized by rapid amplification of cDNA ends polymerase chain reaction (RACE–PCR). A substrate reaction test revealed that AnGolS1 possessed galactinol synthase activity in vitro and could potentially be an early-responsive gene. Furthermore, quantitative real-time PCR (qRT-PCR) indicated that AnGolS1 was responded to cold, salts and drought stresses, however, significantly up-regulated in all origans by low temperatures, especially in plant stems. In addition, the hybridization signals in the fascicular cambium were strongest in all cells under low temperature. Thus, we propose that AnGolS1 plays critical roles in A. nanus low-temperature stress resistance and that fascicular cambium cells could be involved in AnGolS1 mRNA transcription, galactinol transportation and coordination under low-temperature stress. PMID:27786294

  17. Disruption of AP1S1, Causing a Novel Neurocutaneous Syndrome, Perturbs Development of the Skin and Spinal Cord

    PubMed Central

    Drouin, Christian A.; Lapointe, Line; Boudreau, Michèle; Meloche, Caroline; Drouin, Régen; Hudson, Thomas J.; Drapeau, Pierre; Cossette, Patrick

    2008-01-01

    Adaptor protein (AP) complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. Because disruption of the various subunits of the AP complexes is embryonic lethal in the majority of cases, characterization of their function in vivo is still lacking. Here, we describe the first mutation in the human AP1S1 gene, encoding the small subunit σ1A of the AP-1 complex. This founder splice mutation, which leads to a premature stop codon, was found in four families with a unique syndrome characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia (MEDNIK). To validate the pathogenic effect of the mutation, we knocked down Ap1s1 expression in zebrafish using selective antisens morpholino oligonucleotides (AMO). The knockdown phenotype consisted of perturbation in skin formation, reduced pigmentation, and severe motility deficits due to impaired neural network development. Both neural and skin defects were rescued by co-injection of AMO with wild-type (WT) human AP1S1 mRNA, but not by co-injecting the truncated form of AP1S1, consistent with a loss-of-function effect of this mutation. Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord. PMID:19057675

  18. UNUSUAL WATER PRODUCTION ACTIVITY OF COMET C/2012 S1 (ISON): OUTBURSTS AND CONTINUOUS FRAGMENTATION

    SciTech Connect

    Combi, M. R.; Fougere, N.; Mäkinen, J. T. T.; Bertaux, J.-L.; Quémerais, E.

    2014-06-10

    The Solar Wind ANisotropies (SWAN) all-sky hydrogen Lyα camera on the SOlar and Heliospheric Observer (SOHO) satellite observed the hydrogen coma of comet C/2012 S1 (ISON) for most of the last month of its activity from 2013 October 24 to November 24, ending just 4 days before perihelion and its final disruption. The water production rate of the comet was determined from these observations. SOHO has been operating in a halo orbit around the Earth-Sun L1 Lagrange point since its launch in late 1995. Most water vapor produced by comets is ultimately photodissociated into two H atoms and one O atom producing a huge hydrogen coma that is routinely observed in the daily SWAN images in comets of sufficient brightness. Water production rates were calculated from 22 images over most of the last month of the pre-perihelion apparition. The water production rate increased very slowly on average from October 24.9 until November 12.9, staying between 1.8 and 3.4 × 10{sup 28} s{sup –1}, after which it increased dramatically, reaching 1.6 to 2 × 10{sup 30} s{sup –1} from November 21.6 to 23.6. It was not detected after perihelion on December 3.7 when it should have been visible. We examine the active surface area necessary to explain the water production rate and its variation and are able to place constraints on the physical size of the original nucleus necessary to account for the large amount of activity from November 12.9 and until just before perihelion.

  19. Cloud-cloud collision in the Galactic center 50 km s-1 molecular cloud

    NASA Astrophysics Data System (ADS)

    Tsuboi, Masato; Miyazaki, Atsushi; Uehara, Kenta

    2015-12-01

    We performed a search of star-forming sites influenced by external factors, such as SNRs, H II regions, and cloud-cloud collisions (CCCs), to understand the star-forming activity in the Galactic center region using the NRO Galactic Center Survey in SiO v = 0, J = 2-1, H13CO+J = 1-0, and CS J = 1-0 emission lines obtained with the Nobeyama 45 m telescope. We found a half-shell-like feature (HSF) with a high integrated line intensity ratio of ∫TB(SiO v = 0, J = 2-1)dv/∫TB(H13CO+J = 1-0)dv ˜ 6-8 in the 50 km s-1 molecular cloud; the HSF is a most conspicuous molecular cloud in the region and harbors an active star-forming site where several compact H II regions can be seen. The high ratio in the HSF indicates that the cloud contains huge shocked molecular gas. The HSF can be also seen as a half-shell feature in the position-velocity diagram. A hypothesis explaining the chemical and kinetic properties of the HSF is that the feature originates from a CCC. We analyzed the CS J = 1-0 emission line data obtained with the Nobeyama Millimeter Array to reveal the relation between the HSF and the molecular cloud cores in the cloud. We made a cumulative core mass function (CMF) of the molecular cloud cores within the HSF. The CMF in the CCC region is not truncated at least up to ˜2500 M⊙, although the CMF of the non-CCC region reaches the upper limit of ˜1500 M⊙. Most massive molecular cores with Mgas > 750 M⊙ are located only around the ridge of the HSF and adjoin the compact H II region. These may be a sign of massive star formation induced by CCCs in the Galactic center region.

  20. OUTGASSING BEHAVIOR OF C/2012 S1 (ISON) FROM 2011 SEPTEMBER TO 2013 JUNE

    SciTech Connect

    Meech, Karen J.; Yang, Bin; Kleyna, Jan; Chiang, Hsin-Fang; Riesen, Timm; Keane, Jacqueline V.; Reipurth, Bo; Hsieh, Henry H.; Ansdell, Megan; Hainaut, Olivier; Vincent, Jean-Baptiste; Boehnhardt, Hermann; Fitzsimmons, Alan; Rector, Travis; Michaud, Peter; Milani, Giannantonio; Bryssinck, Erik; Ligustri, Rolando; Trabatti, Roberto; Tozzi, Gian-Paolo; and others

    2013-10-20

    We report photometric observations for comet C/2012 S1 (ISON) obtained during the time period immediately after discovery (r = 6.28 AU) until it moved into solar conjunction in mid-2013 June using the UH2.2 m, and Gemini North 8 m telescopes on Mauna Kea, the Lowell 1.8 m in Flagstaff, the Calar Alto 1.2 m telescope in Spain, the VYSOS-5 telescopes on Mauna Loa Hawaii and data from the CARA network. Additional pre-discovery data from the Pan STARRS1 survey extends the light curve back to 2011 September 30 (r = 9.4 AU). The images showed a similar tail morphology due to small micron sized particles throughout 2013. Observations at submillimeter wavelengths using the James Clerk Maxwell Telescope on 15 nights between 2013 March 9 (r = 4.52 AU) and June 16 (r = 3.35 AU) were used to search for CO and HCN rotation lines. No gas was detected, with upper limits for CO ranging between 3.5-4.5 × 10{sup 27} molecules s{sup –1}. Combined with published water production rate estimates we have generated ice sublimation models consistent with the photometric light curve. The inbound light curve is likely controlled by sublimation of CO{sub 2}. At these distances water is not a strong contributor to the outgassing. We also infer that there was a long slow outburst of activity beginning in late 2011 peaking in mid-2013 January (r ∼ 5 AU) at which point the activity decreased again through 2013 June. We suggest that this outburst was driven by CO injecting large water ice grains into the coma. Observations as the comet came out of solar conjunction seem to confirm our models.

  1. Novel alkaline earth copper germanates with ferro and antiferromagnetic S=1/2 chains

    SciTech Connect

    Brandao, Paula; Reis, Mario S; Gai, Zheng; Moreira Dos Santos, Antonio F

    2013-01-01

    Two new alkaline earth copper(II) germanates were hydrothermally synthesized: CaCuGeO4 center dot H2O (1) and BaCu2Ge3O9 center dot H2O (2), and their structures determined by single crystal X-ray diffraction. Compound (1) crystallizes in space group P2(1)/c with a=5.1320(2) angstrom, b=16.1637(5) angstrom, c=5.4818(2) angstrom, beta=102.609(2)degrees, V=443.76(3) angstrom(3) and Z=4. This copper germanate contains layers of composition [CuGeO4](infinity)(2-) comprising CuO4 square planes and GeO4 tetrahedra with calcium and water molecules in the inter-layer space. Compound (2) crystallizes in the Cmcm space group with a=5.5593(3) angstrom, b=10.8606(9) angstrom, c=13.5409(8) angstrom, V=817.56(9) angstrom(3) and Z=4. This structure contains GeO6 and CuO6 octahedra as well as GeO4 tetrahedra, forming a three-dimensional network of interconnecting six-membered ring channels. The magnetic susceptibility for both samples can be interpreted as S=1/2 chains, in agreement with the copper topology observed in the crystal structure. The susceptibility of (1) exhibits a Bonner-Fisher type behavior, resulting from antiferromagnetic intra-chain interactions without three-dimensional ordering down to 5 K-the lowest measured temperature. This observation, together with the absence of super-exchange paths between the copper chains, make this system particularly promising for the study of low dimensional magnetism. The magnetic properties of (2) show a very weak ferromagnetic near-neighbor interaction along the chain. In this compound a peak the chi T plot seems to indicate the onset of interchain antiferromagentic correlations. However, no ordering temperature is detected in the susceptibility data.

  2. Characterization of Samples from Old Solvent Tanks S1 through S22

    SciTech Connect

    Leyba, J.D.

    1999-03-25

    The Old Radioactive Waste Burial Ground (ORWBG, 643-E) contains 22 old solvent tanks (S1 - S22) which were used to receive and store spent PUREX solvent from F- and H-Canyons. The tanks are cylindrical, carbon-steel, single-wall vessels buried at varying depths. A detailed description of the tanks and their history can be found in Reference 1. A Sampling and Analysis Plan for the characterization of the material contained in the old solvent tanks was developed by the Analytical Development Section (ADS) in October of 19972. The Sampling and Analysis Plan identified several potential disposal facilities for the organic and aqueous phases present in the old solvent tanks which included the Solvent Storage Tank Facility (SSTF), the Mixed Waste Storage Facilities (MWSF), Transuranic (TRU) Pad, and/or the Consolidated Incineration Facility (CIF). In addition, the 241-F/H Tank Farms, TRU Pads, and/or the MWSF were identified as potential disposal facilities for the sludge phases present in the tanks. The purpose of this sampling and characterization was to obtain sufficient data on the material present in the old solvent tanks so that a viable path forward could be established for the closure of the tanks. Therefore, the parameters chosen for the characterization of the various materials present in the tanks were based upon the Waste Acceptance Criteria (WAC) of the SSTF3, TRU Pads4, MWSF5, CIF6, and/or 241-F/H Tank Farms7. Several of the WAC's have been revised, canceled, or replaced by new procedures since October of 1997 and hence where required, the results of this characterization program were compared against the latest revision of the appropriate WAC.

  3. Nondestructive post-irradiation examination of Loop-1, S1 and B1 rods

    SciTech Connect

    Bratton, R.L.

    1997-05-01

    As a part of the Pacific Northwest National Laboratory`s Tritium Target Development Program, eleven tritium target rods were irradiated in the Advanced Test Reactor located at the Idaho National Engineering and Environmental Laboratory during 1991. Both nondestructive and destructive post-irradiation examination on all eleven rods was planned under the Tritium Target Development Program. Funding for the program was reduced in 1991 resulting in the early removal of the program experiments before reaching their irradiation goals. Post-irradiation examination was only performed on one of the irradiated rods at the Pacific Northwest National Laboratory before the program was terminated in 1992. On December 6, 1995, the Secretary of Energy announced the pursuit of the Commercial Light-Water Reactor option for producing tritium establishing the Tritium Target Qualification Program at the Pacific Northwest National Laboratory. This program decided to pursue nondestructive and destructive post-irradiation examination of the ten remaining rods from the previous program. The ten rods comprise three experiments. The Loop-1 experiment irradiated eight target rods in a loop configuration for 217 irradiation days. The other two rods were irradiated in two separate irradiation experiments, designated as S1 and B1 for 143 effective full-power days, but at different power levels. After the ten rods were transferred from the ATR Canal to the Hot Fuels Examination Facility, the following examinations were performed: (1) visual examination and photography; (2) neutron radiography; (3) axial gamma scanning; (4) contact profilometry measurement; (5) bow and length measurements; (6) rod puncture and plenum gas analysis/measurement of plenum gas quantity; (7) void volume determination; and (8) internal pressure determination. This report presents the data collected during these examinations.

  4. Pressure broadening and frequency shift of the 5S1/2 → 5D5/2 and 5S1/2 → 7S1/2 two photon transitions in 85Rb by the noble gases and N2

    NASA Astrophysics Data System (ADS)

    Zameroski, Nathan D.; Hager, Gordon D.; Erickson, Christopher J.; Burke, John H.

    2014-11-01

    Doppler free two photon absorption spectroscopy was employed to measure the pressure broadening and frequency shift rates of the 5S1/2 (F = 3) → 5D5/2 (F = 5, 4, 3, 2, 1) (778.105 nm) and the 5S1/2 (F = 2) → 7S1/2 (F = 2) (760.126 nm) two photon transitions in 85Rb by the noble gases and N2. To our knowledge, these rates are reported on for the first time. The self-broadening and shift rate of the 5S1/2 (F = 3) → 5D5/2 (F = 5, 4, 3, 2, 1) transition and self -broadening rate of the 5S1/2 (F = 2) → 7S1/2 (F = 2) transition were also measured. The temperature dependence of the self-frequency shift (Rb-Rb collisions) of these transitions is presented. Helium diffusion rates through Quartz and Pyrex cells are also calculated and the implication of helium diffusion through glass vapor cells is discussed in regards to atomic frequency standards based on these transitions. Experimental pressure broadening and shift rates are compared to theoretically calculated rates assuming a 6, 8 or 6, 8, 10 difference potential and pseudo potential model. Reasonable agreement is achieved between experimental and theoretical values.

  5. Salmonella Typhi OmpS1 and OmpS2 porins are potent protective immunogens with adjuvant properties.

    PubMed

    Moreno-Eutimio, Mario A; Tenorio-Calvo, Alejandra; Pastelin-Palacios, Rodolfo; Perez-Shibayama, Christian; Gil-Cruz, Cristina; López-Santiago, Rubén; Baeza, Isabel; Fernández-Mora, Marcos; Bonifaz, Laura; Isibasi, Armando; Calva, Edmundo; López-Macías, Constantino

    2013-08-01

    Salmonella enterica serovar Typhi (S. Typhi) is the causal agent of typhoid fever, a disease that primarily affects developing countries. Various antigens from this bacterium have been reported to be targets of the immune response. Recently, the S. Typhi genome has been shown to encode two porins--OmpS1 and OmpS2--which are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunizing mice with either OmpS1 or OmpS2 induced production of specific, long-term antibody titres and conferred protection against S. Typhi challenge; in particular, OmpS1 was more immunogenic and conferred greater protective effects than OmpS2. We also found that OmpS1 is a Toll-like receptor 4 (TLR4) agonist, whereas OmpS2 is a TLR2 and TLR4 agonist. Both porins induced the production of tumour necrosis factor and interleukin-6, and OmpS2 was also able to induce interleukin-10 production. Furthermore, OmpS1 induced the over-expression of MHC II molecules in dendritic cells and OmpS2 induced the over-expression of CD40 molecules in macrophages and dendritic cells. Co-immunization of OmpS1 or OmpS2 with ovalbumin (OVA) increased anti-OVA antibody titres, the duration and isotype diversity of the OVA-specific antibody response, and the proliferation of T lymphocytes. These porins also had adjuvant effects on the antibody response when co-immunized with either the Vi capsular antigen from S. Typhi or inactivated 2009 pandemic influenza A(H1N1) virus [A(H1N1)pdm09]. Taken together, the data indicate that OmpS1 and OmpS2, despite being expressed at low levels under in vitro culture conditions, are potent protective immunogens with intrinsic adjuvant properties.

  6. Salmonella Typhi OmpS1 and OmpS2 porins are potent protective immunogens with adjuvant properties

    PubMed Central

    Moreno-Eutimio, Mario A; Tenorio-Calvo, Alejandra; Pastelin-Palacios, Rodolfo; Perez-Shibayama, Christian; Gil-Cruz, Cristina; López-Santiago, Rubén; Baeza, Isabel; Fernández-Mora, Marcos; Bonifaz, Laura; Isibasi, Armando; Calva, Edmundo; López-Macías, Constantino

    2013-01-01

    Salmonella enterica serovar Typhi (S. Typhi) is the causal agent of typhoid fever, a disease that primarily affects developing countries. Various antigens from this bacterium have been reported to be targets of the immune response. Recently, the S. Typhi genome has been shown to encode two porins – OmpS1 and OmpS2 – which are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunizing mice with either OmpS1 or OmpS2 induced production of specific, long-term antibody titres and conferred protection against S. Typhi challenge; in particular, OmpS1 was more immunogenic and conferred greater protective effects than OmpS2. We also found that OmpS1 is a Toll-like receptor 4 (TLR4) agonist, whereas OmpS2 is a TLR2 and TLR4 agonist. Both porins induced the production of tumour necrosis factor and interleukin-6, and OmpS2 was also able to induce interleukin-10 production. Furthermore, OmpS1 induced the over-expression of MHC II molecules in dendritic cells and OmpS2 induced the over-expression of CD40 molecules in macrophages and dendritic cells. Co-immunization of OmpS1 or OmpS2 with ovalbumin (OVA) increased anti-OVA antibody titres, the duration and isotype diversity of the OVA-specific antibody response, and the proliferation of T lymphocytes. These porins also had adjuvant effects on the antibody response when co-immunized with either the Vi capsular antigen from S. Typhi or inactivated 2009 pandemic influenza A(H1N1) virus [A(H1N1)pdm09]. Taken together, the data indicate that OmpS1 and OmpS2, despite being expressed at low levels under in vitro culture conditions, are potent protective immunogens with intrinsic adjuvant properties. PMID:23432484

  7. Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals

    PubMed Central

    Sankhyan, Anurag; Sharma, Chandresh; Dutta, Durgashree; Sharma, Tarang; Chosdol, Kunzang; Wakita, Takaji; Watashi, Koichi; Awasthi, Amit; Acharya, Subrat K.; Khanna, Navin; Tiwari, Ashutosh; Sinha, Subrata

    2016-01-01

    Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21–47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21–47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1-hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants. PMID:26888694

  8. Reduction of Aromatic and Heterocyclic Aromatic N-Hydroxylamines by Human Cytochrome P450 2S1

    PubMed Central

    Wang, Kai; Guengerich, F. Peter

    2013-01-01

    Many aromatic amines and heterocyclic aromatic amines (HAAs) are known carcinogens for animals and there is also strong evidence for some in human cancer. The activation of these compounds, including some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 enzymes (P450) in Family 1 (1A2, 1A1, and 1B1). We previously demonstrated that the bioactivation product of the anti-cancer agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203), an N-hydroxylamine, can be reduced by P450 2S1 to its amine precursor under anaerobic conditions and, to a lesser extent, under aerobic conditions (Wang, K., and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 1740–1751). In the present study, we tested the hypothesis that P450 2S1 is involved in the reductive biotransformation of known carcinogenic aromatic amines and HAAs. The N-hydroxylamines of 4-aminobiphenyl (4-ABP), 2-naphthylamine (2-NA), and 2-aminofluorene (2-AF) were synthesized and found to be reduced by P450 2S1 under both anaerobic and aerobic conditions. The formation of amines due to P450 2S1 reduction also occurred under aerobic conditions but was less apparent because the competitive disproportionation reactions (of the N-hydroxylamines) also yielded amines. Further, some nitroso and nitro derivatives of the arylamines could also be reduced by P450 2S1. None of the amines tested were oxidized by P450 2S1. These results suggest that P450 2S1 may be involved in the reductive detoxication of several of the activated products of carcinogenic aromatic amines and HAAs. PMID:23682735

  9. Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals.

    PubMed

    Sankhyan, Anurag; Sharma, Chandresh; Dutta, Durgashree; Sharma, Tarang; Chosdol, Kunzang; Wakita, Takaji; Watashi, Koichi; Awasthi, Amit; Acharya, Subrat K; Khanna, Navin; Tiwari, Ashutosh; Sinha, Subrata

    2016-02-18

    Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21-47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21-47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1-hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants.

  10. Hypoxia augments outgrowth endothelial cell (OEC) sprouting and directed migration in response to sphingosine-1-phosphate (S1P).

    PubMed

    Williams, Priscilla A; Stilhano, Roberta S; To, Vivian P; Tran, Lyndon; Wong, Kevin; Silva, Eduardo A

    2015-01-01

    Therapeutic angiogenesis provides a promising approach to treat ischemic cardiovascular diseases through the delivery of proangiogenic cells and/or molecules. Outgrowth endothelial cells (OECs) are vascular progenitor cells that are especially suited for therapeutic strategies given their ease of noninvasive isolation from umbilical cord or adult peripheral blood and their potent ability to enhance tissue neovascularization. These cells are recruited to sites of vascular injury or tissue ischemia and directly incorporate within native vascular endothelium to participate in neovessel formation. A better understanding of how OEC activity may be boosted under hypoxia with external stimulation by proangiogenic molecules remains a challenge to improving their therapeutic potential. While vascular endothelial growth factor (VEGF) is widely established as a critical factor for initiating angiogenesis, sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, has recently gained great enthusiasm as a potential mediator in neovascularization strategies. This study tests the hypothesis that hypoxia and the presence of VEGF impact the angiogenic response of OECs to S1P stimulation in vitro. We found that hypoxia altered the dynamically regulated S1P receptor 1 (S1PR1) expression on OECs in the presence of S1P (1.0 μM) and/or VEGF (1.3 nM). The combined stimuli of S1P and VEGF together promoted OEC angiogenic activity as assessed by proliferation, wound healing, 3D sprouting, and directed migration under both normoxia and hypoxia. Hypoxia substantially augmented the response to S1P alone, resulting in ~6.5-fold and ~25-fold increases in sprouting and directed migration, respectively. Overall, this report highlights the importance of establishing hypoxic conditions in vitro when studying ischemia-related angiogenic strategies employing vascular progenitor cells.

  11. Oxidized LDL-induced angiogenesis involves sphingosine 1-phosphate: prevention by anti-S1P antibody

    PubMed Central

    Camaré, Caroline; Trayssac, Magali; Garmy-Susini, Barbara; Mucher, Elodie; Sabbadini, Roger; Salvayre, Robert; Negre-Salvayre, Anne

    2015-01-01

    BACKGROUND AND PURPOSE Neovascularization occurring in atherosclerotic lesions may promote plaque expansion, intraplaque haemorrhage and rupture. Oxidized LDL (oxLDL) are atherogenic, but their angiogenic effect is controversial; both angiogenic and anti-angiogenic effects have been reported. The angiogenic mechanism of oxLDL is partly understood, but the role of the angiogenic sphingolipid, sphingosine 1-phosphate (S1P), in this process is not known. Thus, we investigated whether S1P is involved in the oxLDL-induced angiogenesis and whether an anti-S1P monoclonal antibody can prevent this effect. EXPERIMENTAL APPROACH Angiogenesis was assessed by capillary tube formation by human microvascular endothelial cells (HMEC-1) cultured on Matrigel and in vivo by the Matrigel plug assay in C57BL/6 mice. KEY RESULTS Human oxLDL exhibited a biphasic angiogenic effect on HMEC-1; low concentrations were angiogenic, higher concentrations were cytotoxic. The angiogenic response to oxLDL was blocked by the sphingosine kinase (SPHK) inhibitor, dimethylsphingosine, by SPHK1-siRNA and by an anti-S1P monoclonal antibody. Moreover, inhibition of oxLDL uptake and subsequent redox signalling by anti-CD36 and anti-LOX-1 receptor antibodies and by N-acetylcysteine, respectively, blocked SPHK1 activation and tube formation. In vivo, in the Matrigel plug assay, low concentrations of human oxLDL or murine oxVLDL also triggered angiogenesis, which was prevented by i.p. injection of the anti-S1P antibody. CONCLUSION AND IMPLICATIONS These data highlight the role of S1P in angiogenesis induced by oxLDL both in HMEC-1 cultured on Matrigel and in vivo in the Matrigel plug model in mice, and demonstrate that the anti-S1P antibody effectively blocks the angiogenic effect of oxLDL. PMID:25176316

  12. GW-BSE approach on S1 vertical transition energy of large charge transfer compounds: A performance assessment.

    PubMed

    Ziaei, Vafa; Bredow, Thomas

    2016-11-07

    In this work, we apply many-body perturbation theory (MBPT) on large critical charge transfer (CT) complexes to assess its performance on the S1 excitation energy. Since the S1 energy of CT compounds is heavily dependent on the Hartree-Fock (HF) exchange fraction in the reference density functional, MBPT opens a new way for reliable prediction of CT S1 energy without explicit knowledge of suitable amount of HF-exchange, in contrary to the time-dependent density functional theory (TD-DFT), where depending on various functionals, large errors can arise. Thus, simply by starting from a (semi-)local reference functional and performing update of Kohn-Sham (KS) energies in the Green's function G while keeping dynamical screened interaction (W(ω)) frozen to the mean-field level, we obtain impressingly highly accurate S1 energy at slightly higher computational cost in comparison to TD-DFT. However, this energy-only updating mechanism in G fails to work if the initial guess contains a fraction or 100% HF-exchange, and hence considerably inaccurate S1 energy is predicted. Furthermore, eigenvalue updating both in G and W(ω) overshoots the S1 energy due to enhanced underscreening of W(ω), independent of the (hybrid-)DFT starting orbitals. A full energy-update on top of HF orbitals even further overestimates the S1 energy. An additional update of KS wave functions within the Quasi-Particle Self-Consistent GW (QSGW) deteriorates results, in stark contrast to the good results obtained from QSGW for periodic systems. For the sake of transferability, we further present data of small critical non-charge transfer systems, confirming the outcomes of the CT-systems.

  13. The membrane-associated form of α(s1)-casein interacts with cholesterol-rich detergent-resistant microdomains.

    PubMed

    Le Parc, Annabelle; Honvo Houéto, Edith; Pigat, Natascha; Chat, Sophie; Leonil, Joëlle; Chanat, Eric

    2014-01-01

    Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that α(s1)-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of α(s1)-casein in rat mammary epithelial cells. Using metabolic labelling we show that α(s1)-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of α(s1)-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of α(s1)-casein. These experiments reveal that the insolubility of α(s1)-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of α(s1)-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells.

  14. The Membrane-Associated Form of αs1-Casein Interacts with Cholesterol-Rich Detergent-Resistant Microdomains

    PubMed Central

    Le Parc, Annabelle; Honvo Houéto, Edith; Pigat, Natascha; Chat, Sophie; Leonil, Joëlle; Chanat, Eric

    2014-01-01

    Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that αs1-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of αs1-casein in rat mammary epithelial cells. Using metabolic labelling we show that αs1-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of αs1-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of αs1-casein. These experiments reveal that the insolubility of αs1-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of αs1-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells. PMID:25549363

  15. S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: A preclinical report.

    PubMed

    Chawla, Sonam; Rahar, Babita; Saxena, Shweta

    2016-05-01

    Sphingosine-1-phosphate (S1P) is emerging to have hypoxic preconditioning potential in various preclinical studies. The study aims to evaluate the preclinical preconditioning efficacy of exogenously administered S1P against acute hypobaric hypoxia (HH)-induced pathological disturbances. Male Sprague Dawley rats (200 ± 20 g) were preconditioned with 1, 10, and 100 μg/kg body weight (b.w.) S1P (i.v.) for three consecutive days. On the third day, S1P preconditioned animals, along with hypoxia control animals, were exposed to HH equivalent to 7,620 m (280 mm Hg) for 6 h. Postexposure status of cardiac energy production, circulatory vasoactive mediators, pulmonary and cerebral oxidative damage, and inflammation were assessed. HH exposure led to cardiac energy deficit indicated by low ATP levels and pronounced AMPK activation levels, raised circulatory levels of brain natriuretic peptide and endothelin-1 with respect to total nitrate (NOx), redox imbalance, inflammation, and alterations in NOx levels in the pulmonary and cerebral tissues. These pathological precursors have been routinely reported to be coincident with high-altitude diseases. Preconditioning with S1P, especially 1 µg/kg b.w. dose, was seen to reverse the manifestation of these pathological disturbances. The protective efficacy could be attributed, at least in part, to enhanced activity of cardioprotective protein kinase C and activation of small GTPase Rac1, which led to further induction of hypoxia-adaptive molecular mediators: hypoxia-inducible factor (HIF)-1α and Hsp70. This is a first such report, to the best of our knowledge, elucidating the mechanism of exogenous S1P-mediated HIF-1α/Hsp70 induction. Conclusively, systemic preconditioning with 1 μg/kg b.w. S1P in rats protects against acute HH-induced pathological disturbances. © 2016 IUBMB Life 68(5):365-375, 2016.

  16. GW-BSE approach on S1 vertical transition energy of large charge transfer compounds: A performance assessment

    NASA Astrophysics Data System (ADS)

    Ziaei, Vafa; Bredow, Thomas

    2016-11-01

    In this work, we apply many-body perturbation theory (MBPT) on large critical charge transfer (CT) complexes to assess its performance on the S1 excitation energy. Since the S1 energy of CT compounds is heavily dependent on the Hartree-Fock (HF) exchange fraction in the reference density functional, MBPT opens a new way for reliable prediction of CT S1 energy without explicit knowledge of suitable amount of HF-exchange, in contrary to the time-dependent density functional theory (TD-DFT), where depending on various functionals, large errors can arise. Thus, simply by starting from a (semi-)local reference functional and performing update of Kohn-Sham (KS) energies in the Green's function G while keeping dynamical screened interaction (W(ω)) frozen to the mean-field level, we obtain impressingly highly accurate S1 energy at slightly higher computational cost in comparison to TD-DFT. However, this energy-only updating mechanism in G fails to work if the initial guess contains a fraction or 100% HF-exchange, and hence considerably inaccurate S1 energy is predicted. Furthermore, eigenvalue updating both in G and W(ω) overshoots the S1 energy due to enhanced underscreening of W(ω), independent of the (hybrid-)DFT starting orbitals. A full energy-update on top of HF orbitals even further overestimates the S1 energy. An additional update of KS wave functions within the Quasi-Particle Self-Consistent GW (QSGW) deteriorates results, in stark contrast to the good results obtained from QSGW for periodic systems. For the sake of transferability, we further present data of small critical non-charge transfer systems, confirming the outcomes of the CT-systems.

  17. S1 satellite DNA repetitive units display identical structure and overall variability in all Anatolian brown frog taxa.

    PubMed

    Picariello, Orfeo; Feliciello, Isidoro; Chinali, Gianni

    2016-02-01

    S1 satellite DNA from Palearctic brown frogs has a species-specific structure in all European species. We characterized S1 satellite DNA from the Anatolian brown frogs Rana macrocnemis, R. camerani, and R. holtzi in order to define their taxonomic rank and the structure of this satellite in this frog lineage. Southern blots of genomic DNA digested with KpnI, EcoRV, NdeI, NheI, or StuI produced the same pattern of satellite DNA bands. Moreover, quantitative dot blots showed that this satellite DNA accounts for 0.1 % of the genome in all taxa. Analysis of the overall genomic variability of the S1a repeat sequence in specimens from various populations demonstrated that this repetitive unit also has the same size (476 bp), the same most common sequence (MCS) and the same overall variability in all three taxa, and also in R. macrocnemis tavasensis. The S1a repetitive unit presents three deletions of 9, 8 and 1 bp compared to the 494-bp S1a repeat from European frogs. The S1a MCS has three variable positions (sequence WWTK in positions 183-186), due to the presence of two repeat subpopulations with motifs AATG and WWTT in all taxa. Unlike previously analyzed mitochondrial and nuclear sequences that show considerable variations among these taxa, no difference could be detected in the structure and variability of the S1 satellite repetitive units. This suggests that these taxa should belong to a single species. Our results indicate that this satellite DNA variety probably formed when the Anatolian lineage radiated from common ancestor about 4 mya, and since then has maintained its structure in all four taxa examined.

  18. Influence of residual milk-clotting enzyme on alpha(s1) casein hydrolysis during ripening of Reggianito Argentino cheese.

    PubMed

    Hynes, E R; Aparo, L; Candioti, M C

    2004-03-01

    Milk-clotting enzyme is considered largely denatured after the cooking step in hard cheeses. Nevertheless, typical hydrolysis products derived from rennet action on alpha(s1)-casein have been detected during the ripening of hard cheeses. The aim of the present work was to investigate the influence of residual milk-clotting enzyme on alpha(s1)-casein hydrolysis in Reggianito cheeses. For that purpose, we studied the influence of cooking temperature (45, 52, and 60 degrees C) on milk-clotting enzyme residual activity and alpha(s1)-casein hydrolysis during ripening. Milk-clotting enzyme residual activity in cheeses was assessed using a chromatographic method, and the hydrolysis of alpha(s1)-casein was determined by electrophoresis and high performance liquid chromatography. Milk-clotting enzyme activity was very low or undetectable in 60 degrees C- and 52 degrees C-cooked cheeses at the beginning of the ripening, but it increased afterwards, particularly in 52 degrees C-cooked cheeses. Cheese curds that were cooked at 45 degrees C had higher initial milk clotting activity, but also in this case, there was a later increase. Hydrolysis of alpha(s1)-casein was detected early in cheeses made at 45 degrees C, and later in those made at higher temperatures. The peptide alpha(s1)-I was not detected in 60 degrees C-cooked cheeses. The results suggest that residual milk-clotting enzyme can contribute to proteolysis during ripening of hard cheeses, because it probably renatures partially after the cooking step. Consequently, the production of peptides derived from alpha(s1)-casein in hard cheeses may be at least, partially due to this proteolytic agent.

  19. SUPPLEMENTARY COMPARISON: Final report on Supplementary Comparison APMP.M.H-S1

    NASA Astrophysics Data System (ADS)

    Kongkavitool, Rugkanawan; Hattori, Koichiro; Sanh, Vo; Yen, Lim Gin

    2007-01-01

    This report presents the results of supplementary comparison APMP.M.H-S1 among four national metrology institutes (NIMT, NMIJ/AIST, VMI and SPRING). The comparison was carried out during October 2004 to January 2005 in order to determine the capability of the primary Rockwell hardness standard, including standard conditions, of each participant, to confirm the accuracy of Rockwell hardness scale C measurement declared by the participant, which includes the effect of each participant's primary indenter and determine the degrees of equivalence of hardness scale measurement in the range 20 HRC to 60 HRC. Furthermore, the comparison was carried out a by common indenter, which was provided by the pilot institute, in order to determine the measurement capability of the participant's primary machine without the influence of the indenter, as a study of scientific purpose. The pilot institute was the National Institute of Metrology (Thailand), NIMT. There were two sets of artifacts for the comparison. Each set was composed of nine hardness blocks: 20 HRC, 25 HRC, 30 HRC, 35 HRC, 40 HRC, 45 HRC, 50 HRC, 55 HRC, 60 HRC. The verification of the participant's primary Rockwell hardness machine was carried out according to ISO6508-3 before making the measurement. The pilot institute made measurements at the beginning and the end of the comparison in order to monitor the stability of the artifacts. The degree of equivalence of each national primary hardness standard was expressed quantitatively by two terms, the deviation from KCRV and the uncertainty of this deviation at a 95% level of confidence. The En parameter was calculated to express the equivalence between the measurements of participants as well. The degree of equivalence between pairs of participating institutes was expressed by the difference of their deviations from the key comparison reference value and the uncertainty of this difference at the 95% level of confidence. Main text. To reach the main text of this paper

  20. Observations of comet ISON (C/2012 S1) from Lowell observatory

    SciTech Connect

    Knight, Matthew M.; Schleicher, David G.

    2015-01-01

    We observed the dynamically new sungrazing comet ISON (C/2012 S1) extensively at Lowell Observatory throughout 2013 in order to characterize its behavior prior to perihelion. ISON had “typical” abundances for an Oort Cloud comet. Its dust production, as measured by Afρ, remained nearly constant during the apparition but its CN gas production increased by ∼50 ×. The minimum active area necessary to support observed water production rates exceeded the likely surface area of the nucleus and suggests a population of icy grains in the coma. Together with the flattening of the dust radial profile over time, this is consistant with ejection of a large quantity of slow moving dust and icy grains in the coma at large heliocentric distance. The dust morphology was dominated by the tail, but a faint sunward dust fan was detected in March, April, May, and September. We imaged multiple gas species in September, October, and November. All gas species were more extended than the dust coma, although only CN had sufficient signal-to-noise for detailed morphological study. Excess CN signal was observed in the sunward hemisphere in September and early October. In November the excess CN signal was in the tailward hemisphere and two faint CN features appeared approximately orthogonal to the tail with position angles varying by about ±20° from night to night. Using numerical modeling, we best reproduced the orientation and shape of these features as well as the bulk brightness with a pole oriented approximately toward the Sun and a single source located within ∼35° of the equator. Variations in position angle and relative brightness of the CN features from night to night suggest a rotation period shorter than 24 hr. The production rates and coma morphology suggest a nucleus that was active over nearly its entire sunward facing hemisphere in September and October but which underwent a significant mass loss event, potentially including fragmentation, shortly before November 1

  1. Early pre-perihelion characterization of Comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Li, Jian-Yang; Kelley, M. S.; Farnham, T. L.; A'Hearn, M. F.; Knight, M. M.; Weaver, H. A.; Mutchler, M. J.; Lamy, P.; Toth, I.

    2013-10-01

    Comet C/2012 S1 (ISON) is a dynamically new comet on a sungrazing orbit. As such, C/ISON represents a unique opportunity to study both the cosmic-ray-irradiated surface, produced during the comet's long residence in the Oort cloud, and much deeper layers in the nucleus, exposed when the comet passes 1.7 solar radii from the Sun's surface at perihelion. During the first phase of our investigation, we collected broadband images of C/ISON on April 10, 2012 at a heliocentric distance of 4.15 AU, using the Hubble Space Telescope WFC3/UVIS. We used the F606W and F438W filters in three HST orbits covering a total span of ~19 hrs. The comet shows a well delineated coma in the sunward direction extending about 2" from the nucleus, and a dust tail at least 25" long. The coma has an average red color of 5%/0.1 micron within 1.6" from the nucleus, becoming redder towards the tail. Both the color and the size of the coma in the sunward direction are consistent with outflow of micron sized dust. Broadband photometry yielded Afρ of 1376 cm at 589 nm, and 1281 cm at 433 nm, measured with a 1.6" radius aperture. The total brightness of the comet within a 0.12" radius aperture remained unchanged within 0.03 mag for the entire duration of the observations. A well defined sunward jet is visible after removing the 1/ρ brightness distribution. The jet is centered at position angle 290 deg (E of Celestial N), with a cone angle of 45 deg, a projected length of 1.6", and a slight curvature towards the north near the end. No temporal change in the morphology is observed, suggesting the jet is circumpolar. Under this assumption, the jet’s apparent position constrains the rotational pole to lie within 30 deg of (RA, Dec) = (330, 0), and an obliquity of 50-80 deg. Preliminary analysis using a coma-nucleus separation technique suggests a nuclear radius less than 2 km. The survival of such a small nucleus during its sungrazing perihelion is certainly questionable.

  2. Pre-perihelion characterization of Comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Li, J.; Kelley, M. S.; Farnham, T. L.; A'Hearn, M. F.; Knight, M. M.; Weaver, H. A.; Mutchler, M.; Lamy, P. L.; Toth, I.

    2013-12-01

    Comet C/2012 S1 (ISON) is a dynamically new comet on a sungrazing orbit. As such, C/ISON represents a unique opportunity to study both the cosmic-ray-irradiated surface, produced during the comet's long residence in the Oort cloud, and much deeper layers in the nucleus, exposed when the comet passes within 2 solar radii of the Sun at perihelion. During the first phase of our investigation, we collected broadband images of C/ISON on April 10, 2012 at a heliocentric distance of 4.15 AU, using the Hubble Space Telescope WFC3/UVIS. We used the F606W and F438W filters in three HST orbits covering a total span of ~19 hrs. The comet shows a well delineated coma in the sunward direction extending about 2" from the nucleus, and a dust tail at least 25" long. The coma has an average red color of 5%/0.1 micron within 1.6" from the nucleus, becoming redder towards the tail. Both the color and the size of the coma in the sunward direction are consistent with outflow of micron sized dust. Broadband photometry yielded Afρ of 1376 cm at 589 nm, and 1281 cm at 433 nm, measured with a 1.6" radius aperture. The total brightness of the comet within a 0.12" radius aperture remained unchanged within 0.03 mag for the entire duration of the observations. A well defined sunward jet is visible after removing the 1/ρ brightness distribution. The jet is centered at position angle 290 deg (E of Celestial N), with a cone angle of 45 deg, a projected length of 1.6", and a slight curvature towards the north near the end. No temporal change in the morphology is observed, suggesting the jet is circumpolar. Under this assumption, the jet's apparent position constrains the rotational pole to lie within 30 deg of (RA, Dec) = (330, 0), and an obliquity of 50-80 deg. Preliminary analysis using a coma-nucleus separation technique suggests a nuclear radius less than 2 km. The survival of such a small nucleus during its perihelion at 2.7 solar radii is certainly questionable.

  3. The Anomalous Drift of Comet ISON (C/2012 S1) due to Sublimating Volatiles near Perihelion

    NASA Astrophysics Data System (ADS)

    Steckloff, J. K.; Keane, J. V.; Milam, S.; Coulson, I.; Knight, M. M.

    2014-12-01

    Prior to perihelion passage on 28 November 2013, the observed right ascension (RA) and declination (Dec) coordinates of comet C/2012 S1 (ISON) significantly lagged the predicted JPL (# 53) ephemeris. We show that this "braking effect" is due to a dynamic pressure exerted by sublimating gases on the sunward side of the nucleus [1]. Comet ISON was observed November 23 through November 28 using the SCUBA-2 sub-millimeter camera on the James Clerk Maxwell Telescope (JCMT). Imaging is achieved simultaneously at wavelengths of 850 μm and 450 μm, with RA and Dec determined from the central peak in the coma brightness [2]. When comet ISON was first detected at 850 μm, the 1-mm-sized dust particles were tightly bound to the comet nucleus until at least November 23. Three days later, the dust was less tightly bound, elongated and diffuse, spread out over as much as 120 arc seconds (80,000 km) in the anti-solar direction, suggesting a fragmentation event. We compute the average braking velocity of the nucleus of comet ISON by first measuring the distance between the central RA position and the predicted JPL ephemeris. We then calculate the change in this distance between subsequent observations, and divide this value by the elapsed time between the two observations to yield an average drift velocity of the nucleus over this time interval. We assume that comet ISON, like a number of Jupiter Family Comets visited by spacecraft [3], has low thermal inertia. Thus, the sublimating gases are emitted predominantly on the sunward side of the nucleus. Additionally, we assume that water ice dominates the sublimating gases [4]. We then calculate the pressure on the surface of the nucleus due to the emitted gases using the procedure described in [1]. We match the average drift velocity of the nucleus due to this sublimation pressure with the observed average drift velocity from the JCMT observations, which is sensitive to the size of the body, allowing us to estimate the size of the

  4. Mid-infrared Observation of C/2012 S1 (ISON) with Subaru+COMCIS

    NASA Astrophysics Data System (ADS)

    Ootsubo, T.; Watanabe, J.; Honda, M.; Yanamandra-Fisher, P. A.; Usui, F.; Takita, S.; Kasuga, T.; Furusho, R.; Fuse, T.; Nagashima, M.; Kawakita, H.; Fujiyoshi, T.

    2013-12-01

    Dust grains in comets have been used to investigate the formation conditions of the solar system. A silicate feature is often observed in comets as a 10-micron resonant feature. In most cases the feature shows the existence of crystalline silicate together with amorphous silicate. Since the crystalline silicate grains are generally made through high-temperature annealing above 800K from amorphous ones, it is believed that the crystalline silicate grains produced at the inner part of the disk were transported to the outer cold regions where comet nuclei formed. Comet C/2012 S1 (ISON) is a long-period Oort cloud comet, discovered in September 2012. Mid-IR observations of this new comet and investigation of the 10-micron silicate feature help us to understand the formation of crystalline silicate grains in the early solar nebula. In particular, comet ISON is a sungrazing comet, which is predicted to pass close by the Sun and Earth and becoming a bright object. We might expect possible splitting and exposing of pristine materials inside the nucleus after its perihelion passage. If it splits, we can also investigate the homogeneity of the comet nucleus, and can compare the results with ecliptic comets, such as 9P/Temple and 73P/SW. Even if it does not split, we can fully investigate the evolution of crystalline grains described above. Thus, observations both at pre- and post-pelihelion are indespensable. We have a plan to observe the comet ISON with COMICS (Cooled Mid-Infrared Camera and Spectrometer) mounted on the 8.2m Subaru Telescope on late October 2013 and mid-January 2014. Subaru+COMICS in mid-infrared is a powerful tool for spectroscopic observations of cometary silicate grains. COMICS observations occupy an important place among organized many facilities and science of comet observations. We will conduct imaging and low-dispersion spectroscopic observations in mid-infrared region for the comet. We will show the preliminary result of the observations on October

  5. Mid-infrared observations of sungrazing comet C/2012 S1 (ISON) with the Subaru Telescope

    NASA Astrophysics Data System (ADS)

    Ootsubo, T.; Usui, F.; Takita, S.; Watanabe, J.; Yanamandra-Fisher, P.; Honda, M.; Kawakita, H.; Furusho, R.

    2014-07-01

    Comets are the frozen reservoirs of the early solar nebula and are made of ice and dust. The determination of the properties for cometary dust provides us insight into both the early-solar-nebula environment and the formation process of the planetary system. A silicate feature is often observed in comet spectra in the mid-infrared region and may be used for probing the early history of the solar system. In most cases, the feature shows the existence of crystalline silicate (for example, 11.3 microns) together with amorphous silicate [1,2]. Since the crystallization of silicates from amorphous ones generally requires high-temperature annealing above 800 K (e.g., [3,4]), it is believed that the crystalline silicate grains produced at the inner part of the disk were transported to the outer cold regions where the comet nuclei formed. Comet C/2012 S1 (ISON) is a long-period Oort Cloud comet, discovered in September 2012. In particular, comet ISON is a sungrazing comet, which was predicted to pass close by the Sun and the Earth and becoming a bright object. Mid-infrared observations of this new comet and investigation of the 10-micron silicate feature help us understand the formation of crystalline silicate grains in the early solar nebula. We conducted observations of comet ISON in the mid-infrared wavelength region with the Cooled Mid-Infrared Camera and Spectrometer (COMICS) on the Subaru Telescope on Mauna Kea, Hawaii [5,6,7]. The observation of comet ISON was carried out on 2013 October 19 and 21 UT. Since the weather conditions were not so good when we observed, we carried out N-band imaging observations (8.8 and 12.4 microns) and N-band low-resolution spectroscopy. The spectrum of comet ISON can be fit with the 260--265-K blackbody spectrum when we use the regions of 7.8--8.2 and 12.4--13.0 microns as the continuum. The spectrum has only a weak silicate excess feature, which may be able to attribute to small amorphous olivine grains. We could not detect a clear

  6. Coma in Comet C/2012 S1 (ISON) at ~4 au

    NASA Astrophysics Data System (ADS)

    Videen, Gorden; Zubko, Evgenij; Hines, Dean C.; Shkuratov, Yuriy; Kaydash, Vadym; Muinonen, Karri; Knight, Matthew W.; Sitko, Michael L.; Lisse, Carrey M.; Mutchler, Max; Wooden, Diane H.; Li, Jian-Yang; Kobayashi, Hiroshi

    2015-11-01

    We analyze HST observations of Comet ISON (C/2012 S1) at heliocentric distance ~4 au and phase angle ~12-14 degree. The inner coma (< 5000 km) reveals two polarimetric features, positive degree of linear polarization P = (2.48 ± 0.45)% at projected distances less than 236 km and negative polarization P = - (1.6 ± 0.45)% at 1000 - 5000 km [Hines et al. 2014: ApJL 780, L32]. At these projected distances, average color slope was found to be ~6% per 100 nm [Li et al. 2013: ApJL 779, L3]. When considered simultaneously, these two features place significant constraint on the physical and chemical properties of dust particles [Zubko et al. 2015: Planet. Space Sci., http://dx.doi.org/10.1016/j.pss.2015.08.002].We model this response with agglomerated debris particles, having highly irregular morphology and density of constituent material being consistent with in situ studies of comets. We consider particles of 28 different refractive indices that correspond to in situ studies of comets and plausible assumptions on chemical composition of cometary dust and ices. What emerges from our analysis is that the ISON coma was chemically heterogeneous at the epoch of observation. The positive polarization at small projected distances suggests a high spatial concentration of highly absorbing materials, such as amorphous carbon and/or organics highly irradiated with UV radiation. At larger distances, the negative polarization P = - (1.6 ± 0.45)% and color slope ~6% per 100 nm appear consistent with organics slightly processed with UV radiation, tholins, Mg-Fe silicates, and Mg-rich silicates contaminated with ~10% (by volume) amorphous carbon. A significant abundance of pure water-ice particles and/or pure Mg-rich silicates must be ruled out in this region. These materials have been found in situ in other comets and also detected with imaging polarimetry in the circumnucleus halo regions. Analyses of polarimetric images suggest that Mg-rich silicates could originate from a

  7. LHC constraints and prospects for S1 scalar leptoquark explaining the B ¯→D(*)τ ν ¯ anomaly

    NASA Astrophysics Data System (ADS)

    Dumont, Béranger; Nishiwaki, Kenji; Watanabe, Ryoutaro

    2016-08-01

    Recently, deviations in flavor observables of B ¯→D(*)τ ν ¯ have been shown between the predictions in the Standard Model and the experimental results reported by BABAR, Belle, and LHCb collaborations. One of the solutions to this anomaly is obtained in a class of leptoquark model with a scalar leptoquark boson S1, which is a S U (3 )c triplet and S U (2 )L singlet particle with -1 /3 hypercharge interacting with a quark-lepton pair. With well-adjusted couplings, this model can explain the anomaly and be compatible with all flavor constraints. In such a case, the S1 boson can be pair-produced at CERN's Large Hadron Collider (LHC) and subsequently decay as S1*→t τ , b ντ, and c τ . This paper explores the current 8 and 13 TeV constraints, as well as the detailed prospects at 14 TeV, of this flavor-motivated S1 model. From the current available 8 and 13 TeV LHC searches, we obtain constraints on the S1 boson mass for MS1<400 - 640 GeV depending on values of the leptoquark couplings to fermions. Then we study future prospects for this scenario at the 14 TeV LHC using detailed cut analyses and evaluate exclusion and discovery potentials for the flavor-motivated S1 leptoquark model from searches for the (b ν )(b ¯ν ¯) and (c τ )(c ¯τ ¯) final states. In the latter case, we consider several scenarios for the identification of charm jets. As a result, we find that the S1 leptoquark origin of the B ¯→D(*)τ ν ¯ anomaly can be probed with MS1≲600 /800 GeV at the 14 TeV LHC with L =300 /3000 fb-1 of accumulated data. One can also see that the 14 TeV LHC run II with L =300 fb-1 can exclude the S1 leptoquark boson up to MS1˜0.8TeV at 95% confidence level, whereas a future 14 TeV LHC with L =3000 fb-1 data has a potential to discover the S1 leptoquark boson with its mass up to MS 1˜1.1 TeV with over 5 σ significance, from the (b ν )(b ¯ν ¯) and/or (c τ )(c ¯τ ¯) searches.

  8. Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

    SciTech Connect

    Sudo, Kentaro; Yamaguchi, Taketo . E-mail: yama.take@faculty.chiba-u.jp; Ishihara, Takeshi; Nakamura, Kazuyoshi; Shirai, Yoshihiko; Nakagawa, Akihiko; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Saisho, Hiromitsu

    2007-01-01

    Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m{sup 2}/day. Results: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m{sup 2}/day, 3 at 70 mg/m{sup 2}/day, and 10 at 80 mg/m{sup 2}/day. Though 1 patient at the final dose level (80 mg/m{sup 2}/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m{sup 2}/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.

  9. DMRG Study of the S >= 1 quantum Heisenberg Antiferromagnet on a Kagome-like lattice without loops

    NASA Astrophysics Data System (ADS)

    Lamberty, R. Zach; Changlani, Hitesh J.; Henley, Christopher L.

    2013-03-01

    The Kagome quantum Heisenberg antiferromagnet, for spin up to S = 1 and perhaps S = 3 / 2 , is a prime candidate to realize a quantum spin liquid or valence bond crystal state, but theoretical or computational studies for S > 1 / 2 are difficult and few. We consider instead the same interactions and S >= 1 on the Husimi Cactus, a graph of corner sharing triangles whose centers are vertices of a Bethe lattice, using a DMRG procedure tailored for tree graphs. Since both lattices are locally identical, properties of the Kagome antiferromagnet dominated by nearest-neighbor spin correlations should also be exhibited on the Cactus, whereas loop-dependent effects will be absent on the loopless Cactus. Our study focuses on the possible transition(s) that must occur with increasing S for the Cactus antiferromagnet. (It has a disordered valence bond state at S = 1 / 2 but a 3-sublattice coplanar ordered state in the large S limit). We also investigate the phase diagram of the S = 1 quantum XXZ model with on-site anisotropy, which we expect to have three-sublattice and valence-bond-crystal phases similar to the kagome case. This work is supported by the National Science Foundation through a Graduate Research Fellowship to R. Zach Lamberty, as well as grant DMR-

  10. S1 constrains S4 in the voltage sensor domain of Kv7.1 K+ channels.

    PubMed

    Haitin, Yoni; Yisharel, Ilanit; Malka, Eti; Shamgar, Liora; Schottelndreier, Hella; Peretz, Asher; Paas, Yoav; Attali, Bernard

    2008-04-09

    Voltage-gated K(+) channels comprise a central pore enclosed by four voltage-sensing domains (VSDs). While movement of the S4 helix is known to couple to channel gate opening and closing, the nature of S4 motion is unclear. Here, we substituted S4 residues of Kv7.1 channels by cysteine and recorded whole-cell mutant channel currents in Xenopus oocytes using the two-electrode voltage-clamp technique. In the closed state, disulfide and metal bridges constrain residue S225 (S4) nearby C136 (S1) within the same VSD. In the open state, two neighboring I227 (S4) are constrained at proximity while residue R228 (S4) is confined close to C136 (S1) of an adjacent VSD. Structural modeling predicts that in the closed to open transition, an axial rotation (approximately 190 degrees) and outward translation of S4 (approximately 12 A) is accompanied by VSD rocking. This large sensor motion changes the intra-VSD S1-S4 interaction to an inter-VSD S1-S4 interaction. These constraints provide a ground for cooperative subunit interactions and suggest a key role of the S1 segment in steering S4 motion during Kv7.1 gating.

  11. Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons

    PubMed Central

    Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

    2017-01-01

    The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals. DOI: http://dx.doi.org/10.7554/eLife.21843.001 PMID:28059699

  12. S1PR2 variants associated with auditory function in humans and endocochlear potential decline in mouse

    PubMed Central

    Ingham, Neil J.; Carlisle, Francesca; Pearson, Selina; Lewis, Morag A.; Buniello, Annalisa; Chen, Jing; Isaacson, Rivka L.; Pass, Johanna; White, Jacqueline K.; Dawson, Sally J.; Steel, Karen P.

    2016-01-01

    Progressive hearing loss is very common in the population but we still know little about the underlying pathology. A new spontaneous mouse mutation (stonedeaf, stdf ) leading to recessive, early-onset progressive hearing loss was detected and exome sequencing revealed a Thr289Arg substitution in Sphingosine-1-Phosphate Receptor-2 (S1pr2). Mutants aged 2 weeks had normal hearing sensitivity, but at 4 weeks most showed variable degrees of hearing impairment, which became severe or profound in all mutants by 14 weeks. Endocochlear potential (EP) was normal at 2 weeks old but was reduced by 4 and 8 weeks old in mutants, and the stria vascularis, which generates the EP, showed degenerative changes. Three independent mouse knockout alleles of S1pr2 have been described previously, but this is the first time that a reduced EP has been reported. Genomic markers close to the human S1PR2 gene were significantly associated with auditory thresholds in the 1958 British Birth Cohort (n = 6099), suggesting involvement of S1P signalling in human hearing loss. The finding of early onset loss of EP gives new mechanistic insight into the disease process and suggests that therapies for humans with hearing loss due to S1P signalling defects need to target strial function. PMID:27383011

  13. S1P-Dependent Trafficking of Intracellular Yersinia pestis through Lymph Nodes Establishes Buboes and Systemic Infection

    PubMed Central

    St. John, Ashley L.; Ang, W.X. Gladys; Huang, Min-Nung; Kunder, Christian A.; Chan, Elizabeth W.; Gunn, Michael D.; Abraham, Soman N.

    2015-01-01

    SUMMARY Pathologically swollen lymph nodes (LNs), or buboes, characterize Yersinia pestis infection, yet how they form and function is unknown. We report that colonization of the draining LN (dLN) occurred due to trafficking of infected dendritic cells and monocytes in temporally distinct waves in response to redundant chemotactic signals, including through CCR7, CCR2, and sphingosine-1-phospate (S1P) receptors. Retention of multiple subsets of phagocytes within peripheral LNs using the S1P receptor agonist FTY720 or S1P1-specific agonist SEW2871 increased survival, reduced colonization of downstream LNs, and limited progression to transmission-associated septicemic or pneumonic disease states. Conditional deletion of S1P1 in mononuclear phagocytes abolished node-to-node trafficking of infected cells. Thus, Y. pestis-orchestrated LN remodeling promoted its dissemination via host cells through the lymphatic system but can be blocked by prevention of leukocyte egress from DLNs. These findings define a novel trafficking route of mononuclear phagocytes and identify S1P as a therapeutic target during infection. PMID:25238098

  14. SAR analysis of innovative selective small molecule antagonists of sphingosine-1-phosphate 4 (S1P₄) receptor.

    PubMed

    Urbano, Mariangela; Guerrero, Miguel; Zhao, Jian; Velaparthi, Subash; Schaeffer, Marie-Therese; Brown, Steven; Rosen, Hugh; Roberts, Edward

    2011-09-15

    Recent evidence suggests an innovative application of chemical modulators targeting the S1P(4) receptor as novel mechanism-based drugs for the treatment of influenza virus infection. Modulation of the S1P(4) receptor may also represent an alternative therapeutic approach for clinical conditions where reactive thrombocytosis is an undesired effect or increased megakaryopoiesis is required. With the exception of our recent research program disclosure, we are not aware of any selective S1P(4) antagonists reported in the literature to date. Herein, we describe complementary structure-activity relationships (SAR) of the high-throughput screening (HTS)-derived hit 5-(2,5-dichlorophenyl)-N-(2,6-dimethylphenyl)furan-2-carboxamide and its 2,5-dimethylphenyl analog. Systematic structural modifications of the furan ring showed that both steric and electronic factors in this region have a significant impact on the potency. The furan moiety was successfully replaced with a thiophene or phenyl ring maintaining potency in the low nanomolar range and high selectivity against the other S1P receptor subtypes. By expanding the molecular diversity within the hit-derived class, our SAR study provides innovative small molecule potent and selective S1P(4) antagonists suitable for in vivo pharmacological validation of the target receptor.

  15. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    PubMed

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

  16. Safety and efficacy of stereotactic body radiation therapy combined with S-1 simultaneously followed by sequential S-1 as an initial treatment for locally advanced pancreatic cancer (SILAPANC) trial: study design and rationale of a phase II clinical trial

    PubMed Central

    Zhu, Xiaofei; Ju, Xiaoping; Cao, Fei; Fang, Fang; Qing, Shuiwang; Shen, Yuxin; Jia, Zhen; Cao, Yangsen; Zhang, Huojun

    2016-01-01

    Introduction Upfront surgeries are not beneficial to most patients with pancreatic cancer. Therefore, more emphasis has been placed chemoradiotherapy in locally advanced pancreatic cancer recently. Gemcitabine-based regimens or FOLFIRINOX (a chemotherapy regimen including leucovorin, 5-FU, irinotecan, oxaliplatin) has been proven as a standard chemotherapy in pancreatic cancer. However, severe toxicities may prevent the completion of chemotherapy. S-1 has showed better objective response rates, similar overall survival rates and progression-free survival rates compared with gemcitabine, revealing that S-1 may be a potential candidate in treating pancreatic cancer, especially for patients refractory to gemcitabine. Additionally, stereotactic body radiation therapy with Cyberknife could provide better efficacy than conventional radiotherapy in pancreatic cancer. Therefore, Cyberknife with S-1 simultaneously followed by sequential S-1 as an initial treatment may bring about favourable outcomes but needs further studies. Methods and analysis The S-1 as an initial treatment for locally advanced pancreatic cancer (SILAPANC) trial is a prospective, single-centre, one armed ongoing study. 190 eligible patients are required to initially receive Cyberknife with 1 cycle of S-1 simultaneously. After the concurrent chemoradiotherapy, 2 or 3 cycles of S-1 are sequentially given. Doses and fractions depend on the locations and volumes of tumours and the adjacent organs at risk. S-1 is taken orally, 2 times a day, at a dose of 80 mg/m2 for 28 days, followed by a 14-day interval. The primary objectives are overall survival and 1-year, 2-year, 3-year, 4-year and 5-year overall survival rates. The secondary objectives are cancer-specific survival, progression-free survival, time to progression, local control rates, clinical benefit rates, radiation-induced acute and late toxicities, adverse effects of chemotherapy and quality of life of patients. Besides, variables most

  17. Transcriptional downregulation of S1pr1 is required for establishment of resident memory CD8+ T cells

    PubMed Central

    Skon, Cara N.; Lee, June-Yong; Anderson, Kristin G.; Masopust, David; Hogquist, Kristin A.; Jameson, Stephen C.

    2013-01-01

    Cell-mediated immunity critically depends on lymphocyte localization at sites of infection. While some memory T cells recirculate, a distinct lineage (resident memory T cells; TRM) are embedded in non-lymphoid tissues (NLTs) and mediate potent protective immunity. However, the defining transcriptional basis for TRM establishment is unknown. We report that CD8+ TRM cells lacked expression of the transcription factor KLF2 and its target gene S1pr1 (encoding sphingosine 1-phosphate receptor 1). Forced S1PR1 expression prevented establishment of TRM. Cytokines inducing TRM phenotype (including TGF-β, IL-33 and TNF) provoked KLF2 downregulation in a phosphatidylinositol-3-OH kinase (PI(3)K)–Akt-dependent pathway, suggesting environmental regulation. Hence KLF2 and S1PR1 regulation provides a switch, dictating whether CD8+ T cells commit to the recirculating or tissue resident memory populations. PMID:24162775

  18. Nuclease S1-sensitive sites on superhelical DNA molecules carrying the LTR region of Moloney murine leukemia virus.

    PubMed

    Kimura, T; Takeya, T

    1987-04-29

    The long terminal repeat (LTR) from proviral DNA of Moloney murine leukemia virus (Mo-MLV) was cloned on a derivative of pBR322, and after introducing superhelical torsions into the resulting recombinant, the sites of conformational transition were investigated by the nuclease S1-digestion method. With an increase in the negative linking differences, fourteen dominant cutting sites were identified, of which two were mapped inside the LTR and one at the 3' end of the LTR. By searching the sequence data, all these sites were localized in the regions having either palindromic sequences or AT-rich sequences. Free energy calculation for the local secondary structure on one strand indicated that nuclease S1 attacked the palindromic sequence regions which could form relatively stable hairpin structures. Under the conditions used, no correlation was found between the S1-sensitive sites and the potential Z-DNA-forming regions, including those within the enhancer sequence.

  19. Overlapping resonances interference-induced transparency: the S0 → S2/S1 photoexcitation spectrum of pyrazine.

    PubMed

    Grinev, Timur; Shapiro, Moshe; Brumer, Paul

    2012-09-07

    The phenomenon of "overlapping resonances interference-induced transparency" (ORIT) is introduced and studied in detail for the S(0) → S(2)/S(1) photoexcitation of cold pyrazine (C(4)H(4)N(2)). In ORIT, a molecule becomes transparent at specific wavelengths due to interferences between envelopes of spectral lines displaying overlapping resonances. An example is the S(2) ↔ S(1) internal conversion in pyrazine where destructive interference between overlapping resonances causes the S(0) → S(2)/S(1) light absorption to disappear at certain wavelengths. ORIT may be of practical importance in multi-component mixtures where it would allow for the selective excitation of some molecules in preference to others. Interference-induced cross section enhancement is also shown.

  20. [A Case of Advanced Gastric Cancer with Peritoneal Dissemination Effectively Treated with S-1 and Docetaxel Combination Chemotherapy].

    PubMed

    Saito, Hiroyuki; Suematsu, Yuki; Hiratsuka, Miyuki; Suda, Hiroshi; Takahashi, Miyuki; Omori, Keita; Ishibashi, Yuji; Morita, Akihiko; Wakabayashi, Kazuhiko; Ito, Yutaka

    2015-11-01

    A 72-year-old man underwent surgery for advanced gastric cancer. Systemic chemotherapy was started, using a regimen of S-1/CDDP for 4 courses, followed by 8 courses of S-1. Three years and 8 months after the surgery, abdominal CT demonstrated ascites, and the serum CA19-9 level was abnormally high (1,165.1 U/mL). Adenocarcinoma cells were found in the ascites. Treatment with S-1/docetaxel (DOC) was started. After 10 courses, the ascites disappeared and the serum CA19-9 value returned to normal. Four years and 7 months after the operation, the patient has been in good health, with no signs of recurrence.

  1. Time-resolved photoelectron imaging of ultrafast S2-->S1 internal conversion through conical intersection in pyrazine.

    PubMed

    Suzuki, Yoshi-Ichi; Fuji, Takao; Horio, Takuya; Suzuki, Toshinori

    2010-05-07

    A nonadiabatic electronic transition through a conical intersection was studied by pump-probe photoelectron imaging spectroscopy with a 22 fs time resolution in the benchmark polyatomic molecule of pyrazine and deuterated pyrazine. The lifetimes of the S(2) state of pyrazine and deuterated pyrazine were determined to be 22+/-3 fs by the global fitting of the time-energy maps of photoelectron kinetic energy (PKE) distributions. The lifetime of S(3) was determined to be 40-43 fs. Two-dimensional maps of photoelectron distributions were obtained for time (t) and PKE, and individual PKE distributions upon ionization from S(2) and S(1) were extracted. Quantum beat with an approximately 50 fs period was observed after the S(2)-->S(1) internal conversion, which was attributed to the totally symmetric vibration nu(6a) in S(1).

  2. Programmed hepatocytes cell death associated with FLIP downregulation in response to extracellular preS1/2.

    PubMed

    Rojas, Masyelly D; Peterson, Darrell L; Barboza, Luisa; Terán-Ángel, Guillermo; Labastida-Moreno, Cesar A; Berrueta, Lisbeth; Salmen, Siham

    2014-03-01

    Chronic hepatitis B virus (HBV) infection involves liver damage resulting in continuous cell injury and death. During HBV infection, hepatocytes exhibit changes in death receptor expression and in their susceptibility to death. These changes are observed not only in infected cells but also in bystander cells. Because excess viral surface protein (HBsAg) is secreted in large amounts as soluble particles containing preS proteins, the role of soluble preS1/2 in hepatocyte (HepG2) death modulation is an important issue to be explored. An increase of cell death induced by preS1/2 was observed. Also, cell death was associated with the down-regulation of FLIP and activation of caspase 8, caspase 9, and BID. Additionally, hepatocytes exhibited a sensitization to death mediated by the Fas receptor. These results, may contribute to understanding the role of envelope proteins (preS1/2) in the pathogenesis of HBV infection.

  3. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P).

    PubMed

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-29

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process.

  4. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

    PubMed Central

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-01

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding u